First_id Gene PMID Browse.by.cancer.type Cancer.type Immune.escape.mechanism Evidence.sentences Browse.by.cancer.type_1 Immune.escape.mechanism_1 1 SELP 25309871 Pan-cancer review, pan-cancer Endothelial cell anergy Tumor cell interaction with platelets, leukocytes, and endothelium is mediated mainly by integrins and their ligands and by the binding of P-selectin with selectin ligands expressed on tumor cells. P-selectin binds to a variety of human cancer cells, such as colon, lung, and breast cancer, as well as melanoma and neuroblastoma. Platelets from P-selectin-deficient mice exhibit a reduced interaction with tumor cells, resulting in a marked decrease of metastasis and reflecting the importance of this protein in tumor progression. Pan-cancer Endothelial_cell_anergy 2 SELP 16648968 Pan-cancer review, pan-cancer Endothelial cell anergy Cross-linking of PSGL-1 by P-selectin also primes leukocytes intracellularly for cytokine and chemoattractant-induced beta2-integrin activation for firm adhesion of leukocytes. Furthermore, P-selectin mediates heterotypic aggregation of activated platelets to cancer cells and adhesion of cancer cells to stimulated endothelial cells. Pan-cancer Endothelial_cell_anergy 3 SELL 25309871 Pan-cancer review, pan-cancer Endothelial cell anergy L-selectin is a molecule constitutively expressed on the majority of leukocytes, which enables leukocyte homing to lymphoid organs and extravasation into inflamed tissues. This molecule facilitates tumor metastasis and acts synergistically with P-selectin. Pan-cancer Endothelial_cell_anergy 4 SELL 29272415 Pan-cancer review, pan-cancer Endothelial cell anergy L-selectin binding induces activation of leukocytes, which can be further modulated by selectin-mediated interactions with platelets and endothelial cells. Selectin ligand on leukocytes, PSGL-1, triggers intracellular signaling in leukocytes that are induced through platelet’s P-selectin or endothelial E-selectin binding. Pan-cancer Endothelial_cell_anergy 5 SELL 33708224 Pan-cancer review, pan-cancer Endothelial cell anergy PSGL-1 signaling cascade results in lymphocyte function-associated antigen 1 (LFA-1) activation and engagement with intercellular adhesion molecule 1 (ICAM-1), leading to slow rolling in neutrophils. Interestingly, it has been found that L-selectin is vital to this signaling pathway, as Sell−/− neutrophils failed to phosphorylated SFKs and downstream proteins in vitro, and showed increased rolling velocities and diminished adhesion in vivo. Pan-cancer Endothelial_cell_anergy 6 SBSN 25283635 Renal cancer renal cell carcinoma and melanoma Endothelial cell anergy SBSN expression was higher in isolated human and mouse TEC than in NEC. SBSN knockdown inhibited the migration and tube formation ability of TEC. We also showed that the AKT pathway was a downstream factor of SBSN. Renal_cancer Endothelial_cell_anergy 7 AKT1 25283635 Melanoma renal cell carcinoma and melanoma Endothelial cell anergy Phosphorylation of AKT in mTEC was suppressed by the PI3K inhibitor LY294002 treatment... Moreover, we showed that the protein level of phosphorylated AKT was reduced by siSBSN treatment compared with control siRNA in both types of mTEC (melanoma and renal). Melanoma Endothelial_cell_anergy 8 VEGFA 8695814 Renal cancer renal cell carcinoma Endothelial cell anergy VEGF had largely similar but less prominent effects on TNFa-induced EAM expression as bFGF with the notable exception of the IL-la-induced expression of VCAM-1. Angiogenic factors not only modifies EAM expression but also effectively inhibits HLA-ABC upregulation by IFN-y. It can be concluded from the current study that tumors that are dependent on angiogenesis by their production of angiogenic factors downregulate the inflammatory response of the vascular endothelium Renal_cancer Endothelial_cell_anergy 9 ICAM1 8695814 Renal cancer renal cell carcinoma Endothelial cell anergy Cellular immunity against tumor cells requires adhesion molecules on vascular endothelium that mediate arrest and extravasation of leukocytes into tumors. Endothelial cells (EC) from the vasculature of human solid tumors have a decreased expression of intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 as compared with normal tissue EC. Renal_cancer Endothelial_cell_anergy 10 ICAM2 8695814 Renal cancer renal cell carcinoma Endothelial cell anergy Cellular immunity against tumor cells requires adhesion molecules on vascular endothelium that mediate arrest and extravasation of leukocytes into tumors. Endothelial cells (EC) from the vasculature of human solid tumors have a decreased expression of intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 as compared with normal tissue EC. Renal_cancer Endothelial_cell_anergy 11 FGF2 8695814 Renal cancer renal cell carcinoma Endothelial cell anergy We observed that exposure of normal resting endothelial cells to basic fibroblast growth factor (bFGF) decreases the expression of these EAM both at the protein and RNA level. Pretreatment of HUVEC with 10 ng/mL basic fibroblast growth factor (bFGF) for 3 days before TNFa- or interleukin-la (IL-la) stimulation resulted in ICAM-1 levels of only 30% to 60% of cells without pretreatment Renal_cancer Endothelial_cell_anergy 12 SELE 8695814 Renal cancer renal cell carcinoma Endothelial cell anergy Induction of VCAM-1 and E-selectin, which reaches maximal levels at 6 to 8 hours after activation with TNFα, was also significantly reduced by prior exposure to bFGF. Renal_cancer Endothelial_cell_anergy 13 TNF 8695814 Renal cancer renal cell carcinoma Endothelial cell anergy Induction of VCAM-1 and E-selectin, which reaches maximal levels at 6 to 8 hours after activation with TNFα, was also significantly reduced by prior exposure to bFGF. Renal_cancer Endothelial_cell_anergy 14 VCAM1 8695814 Renal cancer renal cell carcinoma Endothelial cell anergy Induction of VCAM-1 and E-selectin, which reaches maximal levels at 6 to 8 hours after activation with TNFα, was also significantly reduced by prior exposure to bFGF. Renal_cancer Endothelial_cell_anergy 15 LOX 24045659 Renal cancer renal cell carcinoma Endothelial cell anergy LOX is an enzyme that enhances invasion and metastasis of tumor cells. Molecules that are highly expressed in tumor endothelial cells (TECs) may be candidates for specifically targeting TECs. Using DNA microarray analysis, we found that the lysyl oxidase (LOX) gene was upregulated in TECs compared with its expression in normal endothelial cells (NECs). Renal_cancer Endothelial_cell_anergy 16 HAVCR2 30410357 Renal cancer renal cell carcinoma Endothelial cell anergy Endothelial cells can express T-cell immunoglobulin domain and mucin domain (TIM3). TIM-3 inhibited antitumor immunity by mediating T-cell exhaustion. TIM-3+ CD8+ T cells exhibit impaired Stat5 and p38 signaling pathway. Blocking the TIM-3 pathway enhanced cancer immunity and increased the production of interferon-gamma (IFN-γ) in T cells. Renal_cancer Endothelial_cell_anergy 17 EDN1 8630991 Prostate cancer prostate cancer Endothelial cell anergy ET-1 protein expression is detected in situ in 14 of 14 primary cancers and 14 of 16 metastatic sites of human prostatic carcinoma. Prostate_cancer Endothelial_cell_anergy 18 EDNRA 8630991 Prostate cancer prostate cancer Endothelial cell anergy The ET-1-induced prostate cancer cell proliferation was blocked by the addition of the selective ETA antagonist A-127722 but not by the selective ETB antagonist BQ-788. No specific ETC-binding sites could be demonstrated in any established human prostate cancer cell line tested and ETB mRNA detected by reverse transcription PCR was reduced. Prostate_cancer Endothelial_cell_anergy 19 IGF1R 8630991 Prostate cancer prostate cancer Endothelial cell anergy Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. Prostate_cancer Endothelial_cell_anergy 20 PDGFRA 8630991 Prostate cancer prostate cancer Endothelial cell anergy Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. Prostate_cancer Endothelial_cell_anergy 21 IGF2R 8630991 Prostate cancer prostate cancer Endothelial cell anergy Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. Prostate_cancer Endothelial_cell_anergy 22 FGF2 8630991 Prostate cancer prostate cancer Endothelial cell anergy Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. Prostate_cancer Endothelial_cell_anergy 23 EGFR 8630991 Prostate cancer prostate cancer Endothelial cell anergy Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. Prostate_cancer Endothelial_cell_anergy 24 PGF 12019148 Pan-cancer pan-cancer Endothelial cell anergy Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Overexpression of mPlGF leads to increased tumor growth and vascular survival. In addition, PlGF-2 induces survival gene expression and inhibits apoptosis in vitro. Pan-cancer Endothelial_cell_anergy 25 ENG 23074273 Pan-cancer pan-cancer Endothelial cell anergy Endothelial endoglin has a regulatory role in leukocyte trafficking through vascular endothelia. Leukocytes and endothelial cells interact via integrin receptors and endoglin, being this cell adhesion process stimulated by inflammatory stimuli. Pan-cancer Endothelial_cell_anergy 26 FASLG 24793239 Ovarian cancer ovarian cancer Endothelial cell anergy Selective expression of the death mediator Fas ligand (FasL/CD95L) was detected in the vasculature of many human and mouse solid tumors but not in normal vasculature and in these tumors it was associated with scarce CD8+ infiltration and predominance of FoxP3+ T regulatory (Treg) cells. Ovarian_cancer Endothelial_cell_anergy 27 FOXP3 24793239 Ovarian cancer ovarian cancer Endothelial cell anergy Tumor-derived vascular endothelial growth factor A (VEGF-A) interleukin 10 (IL-10) and prostaglandin E2 (PGE2) cooperatively induced FasL expression on endothelial cells, which acquired the ability to kill effector CD8+ T cells but not Treg cells due to higher levels of cFLIP expression in Tregs. Pharmacologic inhibition of VEGF and PGE2 attenuated tumor endothelial FasL expression produced a significant increase in the influx of tumor-rejecting CD8+ over FoxP3+ T cells, which was FasL-dependent and led to CD8-dependent tumor growth suppression. Ovarian_cancer Endothelial_cell_anergy 28 CD8A 24793239 Ovarian cancer ovarian cancer Endothelial cell anergy Tumor-derived vascular endothelial growth factor A (VEGF-A) interleukin 10 (IL-10) and prostaglandin E2 (PGE2) cooperatively induced FasL expression on endothelial cells, which acquired the ability to kill effector CD8+ T cells but not Treg cells due to higher levels of cFLIP expression in Tregs. Pharmacologic inhibition of VEGF and PGE2 attenuated tumor endothelial FasL expression produced a significant increase in the influx of tumor-rejecting CD8+ over FoxP3+ T cells, which was FasL-dependent and led to CD8-dependent tumor growth suppression. Ovarian_cancer Endothelial_cell_anergy 29 VEGFA 24793239 Ovarian cancer ovarian cancer Endothelial cell anergy Tumor-derived vascular endothelial growth factor A (VEGF-A) interleukin 10 (IL-10) and prostaglandin E2 (PGE2) cooperatively induced FasL expression on endothelial cells, which acquired the ability to kill effector CD8+ T cells but not Treg cells due to higher levels of cFLIP expression in Tregs. Pharmacologic inhibition of VEGF and PGE2 attenuated tumor endothelial FasL expression produced a significant increase in the influx of tumor-rejecting CD8+ over FoxP3+ T cells, which was FasL-dependent and led to CD8-dependent tumor growth suppression. Ovarian_cancer Endothelial_cell_anergy 30 IL10 24793239 Ovarian cancer ovarian cancer Endothelial cell anergy Tumor-derived vascular endothelial growth factor A (VEGF-A) interleukin 10 (IL-10) and prostaglandin E2 (PGE2) cooperatively induced FasL expression on endothelial cells, which acquired the ability to kill effector CD8+ T cells but not Treg cells due to higher levels of cFLIP expression in Tregs. Ovarian_cancer Endothelial_cell_anergy 31 MCAM 27065325 Melanoma melanoma, pancreas, prostate, brain, adrenals and colon cancer Endothelial cell anergy sCD146 induces the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. These last effects are mediated in part through the induction and phosphorylation of c-myc in cancer cells. Melanoma Endothelial_cell_anergy 32 MCAM 27065325 Pancreatic cancer melanoma, pancreas, prostate, brain, adrenals and colon cancer Endothelial cell anergy sCD146 induces the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. These last effects are mediated in part through the induction and phosphorylation of c-myc in cancer cells. Pancreatic_cancer Endothelial_cell_anergy 33 MCAM 27065325 Prostate cancer melanoma, pancreas, prostate, brain, adrenals and colon cancer Endothelial cell anergy sCD146 induces the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. These last effects are mediated in part through the induction and phosphorylation of c-myc in cancer cells. Prostate_cancer Endothelial_cell_anergy 34 MCAM 27065325 Brain cancer melanoma, pancreas, prostate, brain, adrenals and colon cancer Endothelial cell anergy sCD146 induces the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. These last effects are mediated in part through the induction and phosphorylation of c-myc in cancer cells. Brain_cancer Endothelial_cell_anergy 35 MCAM 27065325 Other cancers melanoma, pancreas, prostate, brain, adrenals and colon cancer Endothelial cell anergy sCD146 induces the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. These last effects are mediated in part through the induction and phosphorylation of c-myc in cancer cells. Other_cancers Endothelial_cell_anergy 36 MCAM 27065325 Colon cancer melanoma, pancreas, prostate, brain, adrenals and colon cancer Endothelial cell anergy sCD146 induces the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. These last effects are mediated in part through the induction and phosphorylation of c-myc in cancer cells. Colon_cancer Endothelial_cell_anergy 37 ANGPT2 33217955 Melanoma melanoma, glioblastoma, breast cancer, renal cell carcinoma (RCC), and colorectal cancer. Endothelial cell anergy Angiopoietin-2 (ANG2) is another predominant angiogenic factor and cooperative driver of vascular destabilization. ANG2 controls vascular permeability in pathologic conditions and thus acts as a master regulator of vascular stability. ANG2 plays a critical role in the growth and metastasis of tumors by modulating vasculature in the tumor microenvironment. Melanoma Endothelial_cell_anergy 38 ANGPT2 33217955 Brain cancer melanoma, glioblastoma, breast cancer, renal cell carcinoma (RCC), and colorectal cancer. Endothelial cell anergy Angiopoietin-2 (ANG2) is another predominant angiogenic factor and cooperative driver of vascular destabilization. ANG2 controls vascular permeability in pathologic conditions and thus acts as a master regulator of vascular stability. ANG2 plays a critical role in the growth and metastasis of tumors by modulating vasculature in the tumor microenvironment. Brain_cancer Endothelial_cell_anergy 39 ANGPT2 33217955 Breast cancer melanoma, glioblastoma, breast cancer, renal cell carcinoma (RCC), and colorectal cancer. Endothelial cell anergy Angiopoietin-2 (ANG2) is another predominant angiogenic factor and cooperative driver of vascular destabilization. ANG2 controls vascular permeability in pathologic conditions and thus acts as a master regulator of vascular stability. ANG2 plays a critical role in the growth and metastasis of tumors by modulating vasculature in the tumor microenvironment. Breast_cancer Endothelial_cell_anergy 40 ANGPT2 33217955 Renal cancer melanoma, glioblastoma, breast cancer, renal cell carcinoma (RCC), and colorectal cancer. Endothelial cell anergy Angiopoietin-2 (ANG2) is another predominant angiogenic factor and cooperative driver of vascular destabilization. ANG2 controls vascular permeability in pathologic conditions and thus acts as a master regulator of vascular stability. ANG2 plays a critical role in the growth and metastasis of tumors by modulating vasculature in the tumor microenvironment. Renal_cancer Endothelial_cell_anergy 41 ANGPT2 33217955 Colon cancer melanoma, glioblastoma, breast cancer, renal cell carcinoma (RCC), and colorectal cancer. Endothelial cell anergy Angiopoietin-2 (ANG2) is another predominant angiogenic factor and cooperative driver of vascular destabilization. ANG2 controls vascular permeability in pathologic conditions and thus acts as a master regulator of vascular stability. ANG2 plays a critical role in the growth and metastasis of tumors by modulating vasculature in the tumor microenvironment. Colon_cancer Endothelial_cell_anergy 42 STAB1 25320356 Melanoma melanoma and lymphoma Endothelial cell anergy Clever-1/Stabilin-1 is a multifunctional scavenger and adhesion receptor constitutively present on a subset of type II macrophages and lymphatic endothelium. The absence of functional Clever-1, both genetically and therapeutically induced, led to diminished numbers of immunosuppressive leukocyte types in tumors. The use of Clever-1 as a target for modulating immune evasion and lymphatic spread in cancer treatment. Melanoma Endothelial_cell_anergy 43 STAB1 25320356 Lymphoma melanoma and lymphoma Endothelial cell anergy Clever-1/Stabilin-1 is a multifunctional scavenger and adhesion receptor constitutively present on a subset of type II macrophages and lymphatic endothelium. The absence of functional Clever-1, both genetically and therapeutically induced, led to diminished numbers of immunosuppressive leukocyte types in tumors. The use of Clever-1 as a target for modulating immune evasion and lymphatic spread in cancer treatment. Lymphoma Endothelial_cell_anergy 44 PECAM1 29845213 Melanoma melanoma and breast cancer Endothelial cell anergy Endothelial PECAM‑1, through PECAM‑1‑dependent homophilic binding interactions, may induce release of TIMP‑1 from the endothelium into the TME, thus leading to increased tumor cell proliferation Melanoma Endothelial_cell_anergy 45 PECAM1 29845213 Breast cancer melanoma and breast cancer Endothelial cell anergy Endothelial PECAM‑1, through PECAM‑1‑dependent homophilic binding interactions, may induce release of TIMP‑1 from the endothelium into the TME, thus leading to increased tumor cell proliferation Breast_cancer Endothelial_cell_anergy 46 TIMP1 29845213 Melanoma melanoma and breast cancer Endothelial cell anergy TIMP‑1 is also able to promote cell proliferation and survival, including that of tumor cells, independent of MMP inhibition via receptor‑mediated signaling. Melanoma Endothelial_cell_anergy 47 TIMP1 29845213 Breast cancer melanoma and breast cancer Endothelial cell anergy TIMP‑1 is also able to promote cell proliferation and survival, including that of tumor cells, independent of MMP inhibition via receptor‑mediated signaling. Breast_cancer Endothelial_cell_anergy 48 PFKFB3 27866851 Melanoma melanoma Endothelial cell anergy Tumor endothelial cells (ECs) have a hyper-glycolytic metabolism shunting intermediates to nucleotide synthesis. EC haplo-deficiency or blockade of the glycolytic activator PFKFB3 did not affect tumor growth but reduced cancer cell invasion, intravasation, and metastasis by normalizing tumor vessels, which improved vessel maturation and perfusion. Mechanistically, PFKFB3 inhibition tightened the vascular barrier by reducing VE-cadherin endocytosis in ECs and rendering pericytes more quiescent and adhesive (via upregulation of N-cadherin) through glycolysis reduction; it also lowered the expression of cancer cell adhesion molecules in ECs by decreasing NF-κB signaling. PFKFB3-blockade treatment also improved chemotherapy of primary and metastatic tumors. Melanoma Endothelial_cell_anergy 49 BGN 27295191 Melanoma melanoma Endothelial cell anergy Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumor cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Melanoma Endothelial_cell_anergy 50 CD40 32231867 Melanoma melanoma Endothelial cell anergy Gene set enrichment analysis revealed that agonistic CD40 mAb therapy increased interferon (IFN)-related responses in tumor endothelial cells including up-regulation of the immunosuppressive enzyme Indoleamine 2,3-Dioxygenase 1 (IDO1). Melanoma Endothelial_cell_anergy 51 IDO1 32231867 Melanoma melanoma Endothelial cell anergy Tumor endothelial cell up-regulation of IDO1 is an immunosuppressive feed-back mechanism that reduces the response to CD40-stimulating immunotherapy. IDO1 expression was specifically increased in the tumor endothelial pool following anti-CD40 treatment of B16-F10 tumors. Melanoma Endothelial_cell_anergy 52 IFNG 32231867 Melanoma melanoma Endothelial cell anergy Whereas stimulation with the CD40 agonist MegaCD40L did not affect expression of either IDO1 or TRAIL, human recombinant IFNγ treatment elevated IDO1 and TRAIL mRNA expression in a dose-dependent manner. Melanoma Endothelial_cell_anergy 53 STAT1 32231867 Melanoma melanoma Endothelial cell anergy These results are consistent with previous observations demonstrating that the transcription factors STAT1 and IRF1, which are activated in response to IFNγ signaling, bind to the promoter region of IDO1 and regulate gene expression. Melanoma Endothelial_cell_anergy 54 IRF1 32231867 Melanoma melanoma Endothelial cell anergy These results are consistent with previous observations demonstrating that the transcription factors STAT1 and IRF1, which are activated in response to IFNγ signaling, bind to the promoter region of IDO1 and regulate gene expression. Melanoma Endothelial_cell_anergy 55 SELP 24632801 Melanoma Melanoma Endothelial cell anergy Therefore, our findings indicated that P-selectin deficiency inhibited the metastasis of B16 cells and that wild-type platelet refusion reversed this inhibition. The P-selectin-mediated interaction between platelets and B16 cells promoted angiogenesis by up-regulating VEGF. Melanoma Endothelial_cell_anergy 56 CD4 20176801 Lymphoma lymphoma Endothelial cell anergy We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4+ T cells. In vitro, Tim-3+ ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4+ T lymphocytes through the activation of the interleukin-6–STAT3 pathway, inhibiting Th1 polarization and providing protective immunity Lymphoma Endothelial_cell_anergy 57 HAVCR2 20176801 Lymphoma lymphoma Endothelial cell anergy We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4+ T cells. In vitro, Tim-3+ ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4+ T lymphocytes through the activation of the interleukin-6–STAT3 pathway, inhibiting Th1 polarization and providing protective immunity Lymphoma Endothelial_cell_anergy 58 IL6 20176801 Lymphoma lymphoma Endothelial cell anergy We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4+ T cells. In vitro, Tim-3+ ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4+ T lymphocytes through the activation of the interleukin-6–STAT3 pathway, inhibiting Th1 polarization and providing protective immunity Lymphoma Endothelial_cell_anergy 59 STAT3 20176801 Lymphoma lymphoma Endothelial cell anergy We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4+ T cells. In vitro, Tim-3+ ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4+ T lymphocytes through the activation of the interleukin-6–STAT3 pathway, inhibiting Th1 polarization and providing protective immunity Lymphoma Endothelial_cell_anergy 60 IGF1R 27989801 Lymphoma lymphoma Endothelial cell anergy ECs enhance tumor chemoresistance by stimulating the expansion of aggressive CD44+CSF1R+IGF1R+ LCs. Lymphoma Endothelial_cell_anergy 61 IGF1 27989801 Lymphoma lymphoma Endothelial cell anergy IGF1 expressed by TECs stimulates chemoresistance in IGF1R+ TSCs. Indeed liver ECs expressed significantly more IGF1 than ECs from other organs. Lymphoma Endothelial_cell_anergy 62 IGFBP7 27989801 Lymphoma lymphoma Endothelial cell anergy TECs express IGF1R antagonist IGFBP7 to constrain chemoresistance in TSCs. Among all tested IGFBPs, IGFBP7 decreased chemoresistance in LCs co-cultured with ECs. Lymphoma Endothelial_cell_anergy 63 FGF4 27989801 Lymphoma lymphoma Endothelial cell anergy FGF4 derived from aggressive TSCs stimulates FGFR1 in TECs to balance IGF1 and IGFBP7 expression. FGF4 was the most upregulated factor in tumor cells by doxorubicin, 5-FU, and cisplatin chemotherapy. Lymphoma Endothelial_cell_anergy 64 FGFR1 27989801 Lymphoma lymphoma Endothelial cell anergy FGFR1-ETS2 axis modulates IGF1/IGFBP7 expression in TECs. Knockdown of Fgfr1 but not Fgfr2 altered the expression of IGF1 and IGFBP7 in HUVECs. Lymphoma Endothelial_cell_anergy 65 FGF4 24651014 Lymphoma lymphoma Endothelial cell anergy FGF4 produced by B-Cell lymphoma cells (LCs) through activating FGFR1 upregulates the Notchligand Jagged1 (Jag1) on neighboring tumor ECs. In turn, upregulation of Jag1 on ECs reciprocally induces Notch2-Hey1 in LCs. Lymphoma Endothelial_cell_anergy 66 FGFR1 24651014 Lymphoma lymphoma Endothelial cell anergy FGF4 produced by B-Cell lymphoma cells (LCs) through activating FGFR1 upregulates the Notchligand Jagged1 (Jag1) on neighboring tumor ECs. In turn, upregulation of Jag1 on ECs reciprocally induces Notch2-Hey1 in LCs. Lymphoma Endothelial_cell_anergy 67 JAG1 24651014 Lymphoma lymphoma Endothelial cell anergy Upregulation of Jag1 on ECs reciprocally induces Notch2-Hey1 in LCs. Inducible EC-selective deletion of FGFR1 or Jag1 in the Eμ-Myc lymphoma model or impairing Notch2 signaling in mouse and human LCs diminished lymphoma aggressiveness and prolonged mouse survival. Lymphoma Endothelial_cell_anergy 68 NOTCH2 24651014 Lymphoma lymphoma Endothelial cell anergy Inducible EC-selective deletion of FGFR1 or Jag1 in the Eμ-Myc lymphoma model or impairing Notch2 signaling in mouse and human LCs diminished lymphoma aggressiveness and prolonged mouse survival. Lymphoma Endothelial_cell_anergy 69 HEY1 24651014 Lymphoma lymphoma Endothelial cell anergy Co-culture with ECs selectively activates Notch2 in LCs, resulting in Hey1-dependent expansion of LCs. Knockdown of Notch2 or Hey1, or administration of Compound E, significantly reduced hepatic tumor load but Notch1 knockdown had little effect. Thus, juxtacrine activation of Notch2-Hey1 by ECs promotes extra-nodal invasion, a feature of aggressive lymphomas. Lymphoma Endothelial_cell_anergy 70 CD44 24651014 Lymphoma lymphoma Endothelial cell anergy FGF4 produced by B-Cell lymphoma cells (LCs) through activating FGFR1 upregulates the Notchligand Jagged1 (Jag1) on neighboring tumor ECs. In turn, upregulation of Jag1 on ECs reciprocally induces Notch2-Hey1 in LCs. This crosstalk enforces aggressive CD44+IGF1R+CSF1R+ LC phenotypes, including extra-nodal invasion and chemoresistance. Lymphoma Endothelial_cell_anergy 71 IGF1R 24651014 Lymphoma lymphoma Endothelial cell anergy FGF4 produced by B-Cell lymphoma cells (LCs) through activating FGFR1 upregulates the Notchligand Jagged1 (Jag1) on neighboring tumor ECs. In turn, upregulation of Jag1 on ECs reciprocally induces Notch2-Hey1 in LCs. This crosstalk enforces aggressive CD44+IGF1R+CSF1R+ LC phenotypes, including extra-nodal invasion and chemoresistance. Lymphoma Endothelial_cell_anergy 72 CSF1R 24651014 Lymphoma lymphoma Endothelial cell anergy FGF4 produced by B-Cell lymphoma cells (LCs) through activating FGFR1 upregulates the Notchligand Jagged1 (Jag1) on neighboring tumor ECs. In turn, upregulation of Jag1 on ECs reciprocally induces Notch2-Hey1 in LCs. This crosstalk enforces aggressive CD44+IGF1R+CSF1R+ LC phenotypes, including extra-nodal invasion and chemoresistance. Lymphoma Endothelial_cell_anergy 73 PPP3CA 30699351 Lung cancer lung cancer Endothelial cell anergy Bmp2 is identified as a target of the calcineurin/NFAT pathway in lung endothelium, potently inhibiting cancer cell growth by stimulating differentiation. After transduced human umbilical vein ECs (HUVECs) with lentiviruses encoding a constitutively active form of NFATc1 (caNFATc1), there was a 10-fold upregulation of the NFAT target DSCR1 in caNFATc1-HUVECs, thereby confirming the overactivation of NFAT signaling. A significantly increased expression of Tissue Factor and BMP2 is observed. Lung_cancer Endothelial_cell_anergy 74 PPP3CB 30699351 Lung cancer lung cancer Endothelial cell anergy Bmp2 is identified as a target of the calcineurin/NFAT pathway in lung endothelium, potently inhibiting cancer cell growth by stimulating differentiation. After transduced human umbilical vein ECs (HUVECs) with lentiviruses encoding a constitutively active form of NFATc1 (caNFATc1), there was a 10-fold upregulation of the NFAT target DSCR1 in caNFATc1-HUVECs, thereby confirming the overactivation of NFAT signaling. A significantly increased expression of Tissue Factor and BMP2 is observed. Lung_cancer Endothelial_cell_anergy 75 BMP2 30699351 Lung cancer lung cancer Endothelial cell anergy Bmp2 is identified as a target of the calcineurin/NFAT pathway in lung endothelium, potently inhibiting cancer cell growth by stimulating differentiation. After transduced human umbilical vein ECs (HUVECs) with lentiviruses encoding a constitutively active form of NFATc1 (caNFATc1), there was a 10-fold upregulation of the NFAT target DSCR1 in caNFATc1-HUVECs, thereby confirming the overactivation of NFAT signaling. A significantly increased expression of Tissue Factor and BMP2 is observed. Lung_cancer Endothelial_cell_anergy 76 NFATC1 30699351 Lung cancer lung cancer Endothelial cell anergy Bmp2 is identified as a target of the calcineurin/NFAT pathway in lung endothelium, potently inhibiting cancer cell growth by stimulating differentiation. After transduced human umbilical vein ECs (HUVECs) with lentiviruses encoding a constitutively active form of NFATc1 (caNFATc1), there was a 10-fold upregulation of the NFAT target DSCR1 in caNFATc1-HUVECs, thereby confirming the overactivation of NFAT signaling. A significantly increased expression of Tissue Factor and BMP2 is observed. Lung_cancer Endothelial_cell_anergy 77 RCAN1 30699351 Lung cancer lung cancer Endothelial cell anergy Bmp2 is identified as a target of the calcineurin/NFAT pathway in lung endothelium, potently inhibiting cancer cell growth by stimulating differentiation. After transduced human umbilical vein ECs (HUVECs) with lentiviruses encoding a constitutively active form of NFATc1 (caNFATc1), there was a 10-fold upregulation of the NFAT target DSCR1 in caNFATc1-HUVECs, thereby confirming the overactivation of NFAT signaling. A significantly increased expression of Tissue Factor and BMP2 is observed. Lung_cancer Endothelial_cell_anergy 78 EPHA2 21148069 Lung cancer lung cancer Endothelial cell anergy EphA2 negatively regulates Slit2 expression in endothelium, facilitating angiocrine-mediated tumor growth and motility. The data show that slit2 gene expression and Slit activity are elevated in EphA2-deficient endothelium, and suggest that EphA2 negatively regulates slit2 expression in endothelium. Lung_cancer Endothelial_cell_anergy 79 SLIT2 21148069 Lung cancer lung cancer Endothelial cell anergy SLIT2 acts as a tumor suppressive angiocrine factor, with its activity being negatively regulated by endothelial EphA2 receptor. The data show that slit2 gene expression and Slit activity are elevated in EphA2-deficient endothelium, and suggest that EphA2 negatively regulates slit2 expression in endothelium. Lung_cancer Endothelial_cell_anergy 80 ICAM1 7914891 Liver cancer hepatoma Endothelial cell anergy ICAM-1 is an adhesive ligand for the leukocyte integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18). It is a transmembrane glycoprotein that promotes adhesion in immunological and inflammatory reactions. ICAM-1 is expressed on cells of many lineages and is induced by interleukin-6 (IL-6) and interferon-γ (IFN-γ). Liver_cancer Endothelial_cell_anergy 81 IL6 7914891 Liver cancer hepatoma Endothelial cell anergy Functional analysis of ICAM-1 promoter-luciferase constructs in HepG2 cells enabled us to identify a region between -110 and -37 mediating IL-6 and IFN-γ responsiveness and containing a palindromic IL-6/IFN-γ response element (PIRE). Site-directed mutagenesis of key nucleotides in the ICAM-1 PIRE abolished the effect of both IL-6 and IFN-γ stimulation while this PIRE element was sufficient to confer IL-6 and IFN-γ responsiveness to a heterologous promoter. Liver_cancer Endothelial_cell_anergy 82 IFNG 7914891 Liver cancer hepatoma Endothelial cell anergy Functional analysis of ICAM-1 promoter-luciferase constructs in HepG2 cells enabled us to identify a region between -110 and -37 mediating IL-6 and IFN-γ responsiveness and containing a palindromic IL-6/IFN-γ response element (PIRE). Site-directed mutagenesis of key nucleotides in the ICAM-1 PIRE abolished the effect of both IL-6 and IFN-γ stimulation while this PIRE element was sufficient to confer IL-6 and IFN-γ responsiveness to a heterologous promoter. Liver_cancer Endothelial_cell_anergy 83 CD109 7121053 Liver cancer hepatocellular carcinoma Endothelial cell anergy Reduced expression of CD109 on tumor vessels was associated with large tumor size, microvascular invasion, and advanced tumor stage. CD109 knockdown in HUVEC promoted hepatoma cell proliferation, migration, and invasion. Interleukin-8 (IL-8) was a key tumor-promoting factor secreted from CD109 knockdown HUVEC. CD109 knockdown upregulated IL-8 expression through activation of TGF-β/Akt/NF-κB pathway in HUVEC. Liver_cancer Endothelial_cell_anergy 84 CXCL8 7121053 Liver cancer hepatocellular carcinoma Endothelial cell anergy Interleukin-8 (IL-8) was a key tumor-promoting factor secreted from CD109 knockdown HUVEC. CD109 knockdown upregulated IL-8 expression through activation of TGF-β/Akt/NF-κB pathway in HUVEC. CD109 expression on tumor vessels is a potential prognostic marker for HCC, and its reduced expression on TEC promoted tumor progression by paracrine IL-8. Liver_cancer Endothelial_cell_anergy 85 TGFB1 7121053 Liver cancer hepatocellular carcinoma Endothelial cell anergy We further verified that CD109 knockdown upregulated IL-8 expression through activation of TGF-β/Akt/NF-κB pathway in HUVEC. These results were consistent with previous studies showing that activation of TGF-β, Akt, and NF-κB pathways upregulated the IL-8 expression in EC. Liver_cancer Endothelial_cell_anergy 86 AKT1 7121053 Liver cancer hepatocellular carcinoma Endothelial cell anergy We further verified that CD109 knockdown upregulated IL-8 expression through activation of TGF-β/Akt/NF-κB pathway in HUVEC. These results were consistent with previous studies showing that activation of TGF-β, Akt, and NF-κB pathways upregulated the IL-8 expression in EC. Liver_cancer Endothelial_cell_anergy 87 NFKB1 7121053 Liver cancer hepatocellular carcinoma Endothelial cell anergy We further verified that CD109 knockdown upregulated IL-8 expression through activation of TGF-β/Akt/NF-κB pathway in HUVEC. These results were consistent with previous studies showing that activation of TGF-β, Akt, and NF-κB pathways upregulated the IL-8 expression in EC. Liver_cancer Endothelial_cell_anergy 88 EGFR 24045955 Brain cancer glioblastoma Endothelial cell anergy EGFR activation resulted in PKCε- and NF-κB-dependent VCAM-1 up-regulation, which subsequently promoted the interaction between macrophages and GBM cells as well as GBM cell invasion. Brain_cancer Endothelial_cell_anergy 89 EGFR 24045955 Brain cancer glioblastoma Endothelial cell anergy Activated EGF receptor (EGFR) signaling plays an instrumental role in glioblastoma (GBM) progression. Its activation enhances the interaction between macrophages and GBM cells and up-regulates VCAM-1 expression in a PKCε- and NF-κB-dependent manner. EGFR activation in tumor cells was correlated with macrophage infiltration in human GBM specimens. Brain_cancer Endothelial_cell_anergy 90 EGF 24045955 Brain cancer glioblastoma Endothelial cell anergy EGF treatment induced up-regulation of vascular cell adhesion molecule-1 (VCAM-1) expression in a PKCε- and NF-κB-dependent manner. Depletion of VCAM-1 interrupted the binding of macrophages to GBM cells and inhibited EGF-induced and macrophage-promoted GBM cell invasion. Brain_cancer Endothelial_cell_anergy 91 VCAM1 24045955 Brain cancer glioblastoma Endothelial cell anergy EGF treatment induced up-regulation of vascular cell adhesion molecule-1 (VCAM-1) expression in a PKCε- and NF-κB-dependent manner. Depletion of VCAM-1 interrupted the binding of macrophages to GBM cells and inhibited EGF-induced and macrophage-promoted GBM cell invasion. Brain_cancer Endothelial_cell_anergy 92 PRKCE 24045955 Brain cancer glioblastoma Endothelial cell anergy EGFR activation results in PKCε- and NF-κB-dependent VCAM-1 expression. Brain_cancer Endothelial_cell_anergy 93 NFKB1 24045955 Brain cancer glioblastoma Endothelial cell anergy EGFR activation results in PKCε- and NF-κB-dependent VCAM-1 expression. Brain_cancer Endothelial_cell_anergy 94 ANGPT2 26666269 Brain cancer glioblastoma Endothelial cell anergy We identified angiopoietin-2 (Ang-2) as a potential target in both naive and bevacizumab-treated glioblastoma. Ang-2 expression was absent in normal human brain endothelium while the highest Ang-2 levels were observed in bevacizumab-treated GBM. Brain_cancer Endothelial_cell_anergy 95 VEGFA 26666269 Brain cancer glioblastoma Endothelial cell anergy VEGF blockade resulted in endothelial upregulation of Ang-2 whereas the combined inhibition of VEGF and Ang-2 leads to extended survival, decreased vascular permeability, depletion of tumor-associated macrophages, improved pericyte coverage, and increased numbers of intratumoral T lymphocytes. Brain_cancer Endothelial_cell_anergy 96 IL6 29422647 Brain cancer glioblastoma Endothelial cell anergy We identify ECs as one of the major sources for interleukin-6 (IL-6) expression in GBM microenvironment. Furthermore, we reveal that colony-stimulating factor-1 and angiocrine IL-6 induce robust arginase-1 expression and macrophage alternative activation, mediated through peroxisome proliferator-activated receptor-γ-dependent transcriptional activation of hypoxiainducible factor-2α. Brain_cancer Endothelial_cell_anergy 97 HIF1A 29422647 Brain cancer glioblastoma Endothelial cell anergy Short hairpin RNA (shRNA)-mediated HIF-2α knockdown almost completely blocked CSF-1-induced and IL-6-induced arginase-1 protein and mRNA expression and macrophage alternative activation. Together, these data identify a critical role of HIF-2α in CSF-1- induced and IL-6-induced macrophage alternative activation. Brain_cancer Endothelial_cell_anergy 98 CSF1 29422647 Brain cancer glioblastoma Endothelial cell anergy Along with IL-6, CSF-1 induces robust arginase-1 expression and macrophage alternative activation mediated through peroxisome proliferator-activated receptor-γ (PPARγ)-dependent transcriptional activation of HIF-2α. Brain_cancer Endothelial_cell_anergy 99 PPARG 29422647 Brain cancer glioblastoma Endothelial cell anergy PPARγ is required for the transcriptional activation of HIF-2α and arginase-1 expression It is crucial in the alternative activation of macrophages. Brain_cancer Endothelial_cell_anergy 100 ARG1 29422647 Brain cancer glioblastoma Endothelial cell anergy As a critical marker for the antiinflammatory macrophage subset, arginase-1 competes with inducible nitric oxide synthase (iNOS) and hydrolyzes L-arginine into urea and ornithine, a precursor to L-proline and polyamines, which suppress NO-mediated cytotoxicity via L-arginine consumption, enhance collagen synthesis and fibrosis via L-ornithine formation, and increase cellular proliferation via polyamine generation, all important for macrophage-mediated tumor-promoting functions. Brain_cancer Endothelial_cell_anergy 101 NOS3 20144787 Brain cancer glioblastoma Endothelial cell anergy eNOS expression is highly elevated in tumor vascular endothelium adjacent to perivascular glioma cells expressing Nestin, Notch, and the NO receptor sGC. Brain_cancer Endothelial_cell_anergy 102 NES 20144787 Brain cancer glioblastoma Endothelial cell anergy Nestin is expressed by perivascular glioma cells adjacent to eNOS-expressing endothelium. Nestin and Notch are expressed in perivascular glioma cells which also express sGC, indicating these cells can respond to NO signaling. Brain_cancer Endothelial_cell_anergy 103 NOTCH1 20144787 Brain cancer glioblastoma Endothelial cell anergy Nestin and Notch are expressed in perivascular glioma cells which also express sGC, indicating these cells can respond to NO signaling. Brain_cancer Endothelial_cell_anergy 104 SGCB 20144787 Brain cancer glioblastoma Endothelial cell anergy Nestin and Notch are expressed in perivascular glioma cells which also express sGC, indicating these cells can respond to NO signaling. Brain_cancer Endothelial_cell_anergy 105 PRKG1 20144787 Brain cancer glioblastoma Endothelial cell anergy The NO/cGMP/PKG pathway drives Notch signaling in PDGF-induced gliomas in vitro and induces the side population phenotype in primary glioma cell cultures. Brain_cancer Endothelial_cell_anergy 106 PDGFD 24962027 Brain cancer glioblastoma Endothelial cell anergy PDGF induced NO synthesis in GICs. Upon PDGF treatment, NOS2 and NOS3 mRNA levels increased in all five GICs tested, and NOS2 protein elevated in all three GICs tested. Depletion of NOS2 and NOS3 expression in GICs by siRNAs deceased ID4 expression levels. Brain_cancer Endothelial_cell_anergy 107 NOS2 24962027 Brain cancer glioblastoma Endothelial cell anergy PDGF induced NO synthesis in GICs. Upon PDGF treatment, NOS2 and NOS3 mRNA levels increased in all five GICs tested, and NOS2 protein elevated in all three GICs tested. Depletion of NOS2 and NOS3 expression in GICs by siRNAs deceased ID4 expression levels. Brain_cancer Endothelial_cell_anergy 108 NOS3 24962027 Brain cancer glioblastoma Endothelial cell anergy PDGF induced NO synthesis in GICs. Upon PDGF treatment, NOS2 and NOS3 mRNA levels increased in all five GICs tested, and NOS2 protein elevated in all three GICs tested. Depletion of NOS2 and NOS3 expression in GICs by siRNAs deceased ID4 expression levels. Brain_cancer Endothelial_cell_anergy 109 ID4 24962027 Brain cancer glioblastoma Endothelial cell anergy ID4 functions as a key regulator in connecting PDGF signaling and NO activity in GICs and tumor endothelium. ID4 and JAGGED1 protein levels increased significantly at 3 and 12 hours after PDGF treatment in X02, X03, and GSC1T GICs. Depletion of NOS2 and NOS3 expression in GICs by siRNAs deceased ID4 expression levels Brain_cancer Endothelial_cell_anergy 110 JAG1 24962027 Brain cancer glioblastoma Endothelial cell anergy JAGGED1 is involved in the activation of NOTCH signaling by ID4, which is crucial for GIC self-renewal and tumor progression. ID4 and JAGGED1 protein levels increased significantly at 3 and 12 hours after PDGF treatment in X02, X03, and GSC1T GICs. Depletion of NOS2 and NOS3 expression in GICs by siRNAs deceased ID4 expression levels Brain_cancer Endothelial_cell_anergy 111 NOTCH1 24962027 Brain cancer glioblastoma Endothelial cell anergy NOTCH signaling plays a critical role in inducing angiogenesis in the tumor microenvironment and maintaining stem cell traits in GICs. Brain_cancer Endothelial_cell_anergy 112 BHLHA15 26585400 Gastrointestinal cancer gastric cancer Endothelial cell anergy Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1+ stem cells can originate intestinal-type cancer with Kras and Apc mutation and diffuse-type cancer with the loss of E-cadherin (Cdh1). Gastrointestinal_cancer Endothelial_cell_anergy 113 KRAS 26585400 Gastrointestinal cancer gastric cancer Endothelial cell anergy Mist1+ stem cells can originate intestinal-type cancer with Kras and Apc mutation and diffuse-type cancer with the loss of E-cadherin (Cdh1). Gastrointestinal_cancer Endothelial_cell_anergy 114 APC 26585400 Gastrointestinal cancer gastric cancer Endothelial cell anergy Mist1+ stem cells can originate intestinal-type cancer with Kras and Apc mutation and diffuse-type cancer with the loss of E-cadherin (Cdh1). Gastrointestinal_cancer Endothelial_cell_anergy 115 CDH1 26585400 Gastrointestinal cancer gastric cancer Endothelial cell anergy Mist1+ stem cells can originate intestinal-type cancer with Kras and Apc mutation and diffuse-type cancer with the loss of E-cadherin (Cdh1). Gastrointestinal_cancer Endothelial_cell_anergy 116 CXCL12 26585400 Gastrointestinal cancer gastric cancer Endothelial cell anergy Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs), which are enriched in the perivascular region of the isthmus, form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in E-cadherin-depleted cells. Gastrointestinal_cancer Endothelial_cell_anergy 117 CXCR4 26585400 Gastrointestinal cancer gastric cancer Endothelial cell anergy Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs), which are enriched in the perivascular region of the isthmus, form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in E-cadherin-depleted cells. Gastrointestinal_cancer Endothelial_cell_anergy 118 WNT5A 26585400 Gastrointestinal cancer gastric cancer Endothelial cell anergy Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs), which are enriched in the perivascular region of the isthmus, form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in E-cadherin-depleted cells. Gastrointestinal_cancer Endothelial_cell_anergy 119 RHOA 26585400 Gastrointestinal cancer gastric cancer Endothelial cell anergy Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs), which are enriched in the perivascular region of the isthmus, form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in E-cadherin-depleted cells. Gastrointestinal_cancer Endothelial_cell_anergy 120 ICAM1 12727857 Colon cancer colon carcinoma Endothelial cell anergy ICAM-1 expression was found to be down-regulated in tumor-associated endothelium as compared with ECs obtained from normal tissue. Colon_cancer Endothelial_cell_anergy 121 VCAM1 12727857 Colon cancer colon carcinoma Endothelial cell anergy In cultured b.END5 cells, the tumor necrosis factor α (TNF-α)-induced up-regulation of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 was reduced in ECs that were preincubated with basic fibroblast growth factor or vascular endothelial growth factor. Colon_cancer Endothelial_cell_anergy 122 FGF2 12727857 Colon cancer colon carcinoma Endothelial cell anergy bFGF influences the expression of endothelial adhesion molecules and affecting leukocyte interactions with the vessel wall. It was observed to down-regulate ICAM-1 on freshly isolated ECs in a dose-dependent manner. Colon_cancer Endothelial_cell_anergy 123 STING1 31343989 Colon cancer colon and breast cancer Endothelial cell anergy STING is expressed in endothelial cells of normal and tumor tissues and its activation leads to the production of type I IFNs and enhances CD8+ T cell crosspriming, inducing adaptive anticancer immune responses. STING activation with agonists normalized tumor vasculatures in implanted and spontaneous cancers through upregulation of type I/II IFN genes and vascular stabilizing genes (e.g., Angpt1, Pdgfrb, and Col4a). The effects were dependent on type I IFN signaling and CD8+ T cells, demonstrating therapeutic efficacy when combined with VEGFR2 blockade and immune-checkpoint blockade. Colon_cancer Endothelial_cell_anergy 124 STING1 31343989 Breast cancer colon and breast cancer Endothelial cell anergy STING is expressed in endothelial cells of normal and tumor tissues and its activation leads to the production of type I IFNs and enhances CD8+ T cell crosspriming, inducing adaptive anticancer immune responses. STING activation with agonists normalized tumor vasculatures in implanted and spontaneous cancers through upregulation of type I/II IFN genes and vascular stabilizing genes (e.g., Angpt1, Pdgfrb, and Col4a). The effects were dependent on type I IFN signaling and CD8+ T cells, demonstrating therapeutic efficacy when combined with VEGFR2 blockade and immune-checkpoint blockade. Breast_cancer Endothelial_cell_anergy 125 KDR 31343989 Colon cancer colon and breast cancer Endothelial cell anergy The blockade of VEGFR2 in combination with STING activation led to enhanced therapeutic effects, including complete regression of immunotherapy-resistant tumors. Colon_cancer Endothelial_cell_anergy 126 KDR 31343989 Breast cancer colon and breast cancer Endothelial cell anergy The blockade of VEGFR2 in combination with STING activation led to enhanced therapeutic effects, including complete regression of immunotherapy-resistant tumors. Breast_cancer Endothelial_cell_anergy 127 CD274 28404866 Breast cancer breast cancer and pancreatic cancer Endothelial cell anergy Successful treatment with a combination of anti-VEGFR2 and anti–PD-L1 antibodies induced high endothelial venules (HEVs) in PyMT (polyoma middle T oncoprotein) breast cancer and RT2-PNET (Rip1-Tag2 pancreatic neuroendocrine tumors), but not in glioblastoma (GBM). These HEVs promoted lymphocyte infiltration and activity through activation of lymphotoxin β receptor (LTβR) signaling. Breast_cancer Endothelial_cell_anergy 128 CD274 28404866 Pancreatic cancer breast cancer and pancreatic cancer Endothelial cell anergy Successful treatment with a combination of anti-VEGFR2 and anti–PD-L1 antibodies induced high endothelial venules (HEVs) in PyMT (polyoma middle T oncoprotein) breast cancer and RT2-PNET (Rip1-Tag2 pancreatic neuroendocrine tumors), but not in glioblastoma (GBM). These HEVs promoted lymphocyte infiltration and activity through activation of lymphotoxin β receptor (LTβR) signaling. Pancreatic_cancer Endothelial_cell_anergy 129 GPER1 29212519 Breast cancer breast cancer Endothelial cell anergy GPER is a transcriptional target of hypoxia-inducible factor 1 alpha (HIF-1α) and activates VEGF expression and angiogenesis in hypoxic breast tumor microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic effects, has been shown to activate GPER in breast cancer cells. Breast_cancer Endothelial_cell_anergy 130 IGF1R 29212519 Breast cancer breast cancer Endothelial cell anergy GPER is a transcriptional target of hypoxia-inducible factor 1 alpha (HIF-1α) and activates VEGF expression and angiogenesis in hypoxic breast tumor microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic effects, has been shown to activate GPER in breast cancer cells. Breast_cancer Endothelial_cell_anergy 131 IGF1 29212519 Breast cancer breast cancer Endothelial cell anergy IGF1/IGF1R signaling engages the ERK1/2 and AKT transduction pathways to induce the expression of HIF-1α and its targets GPER and VEGF. A functional cooperation between HIF-1α and GPER is essential for the transcriptional activation of VEGF induced by IGF1. Breast_cancer Endothelial_cell_anergy 132 HIF1A 29212519 Breast cancer breast cancer Endothelial cell anergy IGF1/IGF1R signaling engages the ERK1/2 and AKT transduction pathways to induce the expression of HIF-1α and its targets GPER and VEGF. A functional cooperation between HIF-1α and GPER is essential for the transcriptional activation of VEGF induced by IGF1. Breast_cancer Endothelial_cell_anergy 133 VEGFA 29212519 Breast cancer breast cancer Endothelial cell anergy IGF1/IGF1R signaling engages the ERK1/2 and AKT transduction pathways to induce the expression of HIF-1α and its targets GPER and VEGF. A functional cooperation between HIF-1α and GPER is essential for the transcriptional activation of VEGF induced by IGF1. Breast_cancer Endothelial_cell_anergy 134 AKT1 29212519 Breast cancer breast cancer Endothelial cell anergy IGF1/IGF1R signaling engages the ERK1/2 and AKT transduction pathways to induce the expression of HIF-1α and its targets GPER and VEGF. A functional cooperation between HIF-1α and GPER is essential for the transcriptional activation of VEGF induced by IGF1. Breast_cancer Endothelial_cell_anergy 135 TGFB1 25623554 Breast cancer Breast cancer Endothelial cell anergy The western analysis showed Smad5 phosphorylation only in response to treating ECsNorm with Jag1 and TGFβ ligands as was compared with total Smad5 protein. To further verify the synergistic role of Jag1/notch and TGFβ/Smad5 in this process, they treated ECsNorm with both Jag1 and TGFβ ligands and observed increased level of Smad5 phosphorylation confirming the synergistic role for the ligands in activation of Smad5. Breast_cancer Endothelial_cell_anergy 136 JAG1 25623554 Breast cancer Breast cancer Endothelial cell anergy ECsMes acquired prolonged survival, increased migratory behavior, and enhanced angiogenic properties. The mesenchymal phenotypes in ECsMes resulted from a contact-dependent transient phenomenon and were regulated by a synergistic role of the Notch and TGFβ pathways. The western analysis showed Smad5 phosphorylation only in response to treating ECsNorm with Jag1 and TGFβ ligands as was compared with total Smad5 protein. Breast_cancer Endothelial_cell_anergy 137 SMAD5 25623554 Breast cancer Breast cancer Endothelial cell anergy ECsMes acquired prolonged survival, increased migratory behavior, and enhanced angiogenic properties. The mesenchymal phenotypes in ECsMes resulted from a contact-dependent transient phenomenon and were regulated by a synergistic role of the Notch and TGFβ pathways. The western analysis showed Smad5 phosphorylation only in response to treating ECsNorm with Jag1 and TGFβ ligands as was compared with total Smad5 protein. Breast_cancer Endothelial_cell_anergy 138 LGALS1 29602445 Breast cancer Breast cancer Endothelial cell anergy Galectin-1 in endothelial cells contributes to tumor progression by controlling vascular endothelial and lymphatic endothelial cell programs, modulating angiogenesis and lymphangiogenesis through different signaling pathways and receptors, including VEGFR2, VEGFR3, neuropilin-1, and podoplanin. Breast_cancer Endothelial_cell_anergy 139 LGALS3 29602445 Breast cancer Breast cancer Endothelial cell anergy Gal-3 also binds and activates VEGFR2 in ECs, inducing VEGFR2 phosphorylation. Knocking down Gal-3 or MGAT5 reduced VEGF-A-mediated angiogenesis. Therefore, Gal-3 modulates EC biology by directly interacting with VEGFR2 Nglycans and increasing the angiogenic response to its canonical ligand. Breast_cancer Endothelial_cell_anergy 140 LGALS8 29602445 Breast cancer Breast cancer Endothelial cell anergy Gal-8 is one of the most prominent galectins found in ECs. Either exogenously added or endogenously regulated, this two-CRD galectin promotes EC migration and capillary tube formation, and facilitates angiogenesis in vivo. Breast_cancer Endothelial_cell_anergy 141 EGFL7 22037871 Breast cancer breast and lung carcinoma Endothelial cell anergy EGFL7 is expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels correlate with higher tumor grade and poorer prognosis. Expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice by inhibiting the expression of leukocyte adhesion molecules (ICAM-1 and VCAM-1) by endothelial cells, thus preventing lymphocyte adhesion and reducing immune cell infiltration into the tumor. Breast_cancer Endothelial_cell_anergy 142 EGFL7 22037871 Lung cancer breast and lung carcinoma Endothelial cell anergy EGFL7 is expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels correlate with higher tumor grade and poorer prognosis. Expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice by inhibiting the expression of leukocyte adhesion molecules (ICAM-1 and VCAM-1) by endothelial cells, thus preventing lymphocyte adhesion and reducing immune cell infiltration into the tumor. Lung_cancer Endothelial_cell_anergy 143 ICAM1 22037871 Breast cancer breast and lung carcinoma Endothelial cell anergy The expression of ICAM-1 and VCAM-1 is inhibited by Egfl7, leading to reduced infiltration of immune cells into tumors and characterized by lower levels of immunostimulatory cytokines (IFN-γ and IL-12). Breast_cancer Endothelial_cell_anergy 144 ICAM1 22037871 Lung cancer breast and lung carcinoma Endothelial cell anergy The expression of ICAM-1 and VCAM-1 is inhibited by Egfl7, leading to reduced infiltration of immune cells into tumors and characterized by lower levels of immunostimulatory cytokines (IFN-γ and IL-12). Lung_cancer Endothelial_cell_anergy 145 VCAM1 22037871 Breast cancer breast and lung carcinoma Endothelial cell anergy The expression of ICAM-1 and VCAM-1 is inhibited by Egfl7, leading to reduced infiltration of immune cells into tumors and characterized by lower levels of immunostimulatory cytokines (IFN-γ and IL-12). Breast_cancer Endothelial_cell_anergy 146 VCAM1 22037871 Lung cancer breast and lung carcinoma Endothelial cell anergy The expression of ICAM-1 and VCAM-1 is inhibited by Egfl7, leading to reduced infiltration of immune cells into tumors and characterized by lower levels of immunostimulatory cytokines (IFN-γ and IL-12). Lung_cancer Endothelial_cell_anergy 147 CXCL10 25361735 Melanoma melanoma Endothelial cell anergy Our results demonstrate a novel role of VEGF in negative regulation of NF-kB signaling and endothelial activation in the tumor microenvironment and provide evidence that pharmacological inhibition of VEGF signaling enhances T-lymphocyte recruitment through up-regulation of chemokine CXCL10 and CXCL11. Melanoma Endothelial_cell_anergy 148 CXCL11 25361735 Melanoma melanoma Endothelial cell anergy Our results demonstrate a novel role of VEGF in negative regulation of NF-kB signaling and endothelial activation in the tumor microenvironment and provide evidence that pharmacological inhibition of VEGF signaling enhances T-lymphocyte recruitment through up-regulation of chemokine CXCL10 and CXCL11. Melanoma Endothelial_cell_anergy 149 VCAN 38517140 Breast cancer breast cancer Matrix barrier Overall, we conclude that VCAN can either support or inhibit T-cell trafficking within the tumor microenvironment depending on the pattern of GAGs present, and that VCAN is a major component of the ECM immunologic barrier that defines the type of response to immunotherapy. Breast_cancer Matrix_barrier 150 CD93 38441970 Melanoma melanoma Matrix barrier Here, we demonstrate that CD93 participates in maintaining the endothelial barrier and reducing metastatic dissemination. Primary melanoma growth was hampered in CD93-/- mice, but metastatic dissemination was increased and associated with disruption of adherents and tight junctions in tumor endothelial cells and elevated expression of matrix metalloprotease 9 at the metastatic site. Melanoma Matrix_barrier 151 KDR 38441970 Melanoma melanoma Matrix barrier CD93 directly interacted with vascular endothelial growth factor receptor 2 (VEGFR2) and its absence led to VEGF-induced hyperphosphorylation of VEGFR2 in endothelial cells. Antagonistic anti-VEGFR2 antibody therapy rescued endothelial barrier function and reduced the metastatic burden in CD93-/- mice to wild-type levels. Melanoma Matrix_barrier 152 EIF4A3 38345073 Brain cancer glioblastoma multiforme Matrix barrier EIF4A3 promotes the expression of several non-coding RNAs, viz, Circ matrix metallopeptidase 9 (MMP9), a prominent oncogene, by interacting with the upstream region of the circMMP9 mRNA transcript and acts on cell proliferation, migration, and invasion of GBM. Brain_cancer Matrix_barrier 153 MMP9 38345073 Brain cancer glioblastoma multiforme Matrix barrier EIF4A3 promotes the expression of several non-coding RNAs, viz, Circ matrix metallopeptidase 9 (MMP9), a prominent oncogene, by interacting with the upstream region of the circMMP9 mRNA transcript and acts on cell proliferation, migration, and invasion of GBM. Brain_cancer Matrix_barrier 154 PTK2 38291516 Lung cancer lung adenocarcinoma Matrix barrier FAK inhibition with a small molecular inhibitor could remodel the TME by inhibiting CAFs activation, decreasing collagen deposition and further facilitating the infiltration of anti-tumor immune cells, including CD8+ T cells, DC cells and M1-like macrophages into tumors, hence, converting "immune-cold" KL tumors into "immune-hot" tumors. Lung_cancer Matrix_barrier 155 HYAL1 38284224 Breast cancer breast cancer, melanoma and prostate cancer Matrix barrier Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Breast_cancer Matrix_barrier 156 HYAL1 38284224 Melanoma breast cancer, melanoma and prostate cancer Matrix barrier Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Melanoma Matrix_barrier 157 HYAL1 38284224 Prostate cancer breast cancer, melanoma and prostate cancer Matrix barrier Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Prostate_cancer Matrix_barrier 158 HYAL2 38284224 Breast cancer breast cancer, melanoma and prostate cancer Matrix barrier Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Breast_cancer Matrix_barrier 159 HYAL2 38284224 Melanoma breast cancer, melanoma and prostate cancer Matrix barrier Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Melanoma Matrix_barrier 160 HYAL2 38284224 Prostate cancer breast cancer, melanoma and prostate cancer Matrix barrier Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Prostate_cancer Matrix_barrier 161 HAVCR2 38225927 Pan-cancer Pan-Cancer Matrix barrier ECM-related cancer-associated fibroblasts enriched at the tumor boundary acted as a barrier to exclude immune cells, interacted with malignant cells to promote tumor progression, and regulated exhausted CD8+ T cells via immune checkpoint ligand-receptors (e.g., LGALS9/TIM-3) to promote immune escape. Pan-cancer Matrix_barrier 162 LGALS9 38225927 Pan-cancer Pan-Cancer Matrix barrier ECM-related cancer-associated fibroblasts enriched at the tumor boundary acted as a barrier to exclude immune cells, interacted with malignant cells to promote tumor progression, and regulated exhausted CD8+ T cells via immune checkpoint ligand-receptors (e.g., LGALS9/TIM-3) to promote immune escape. Pan-cancer Matrix_barrier 163 FABP4 38225927 Pan-cancer Pan-Cancer Matrix barrier Fibrogenic and vascular pericytes (PC) derived from FABP4+ progenitors were two distinct tumor-associated PC subpopulations that strongly interacted with PGF+ tips, resulting in excess extracellular matrix (ECM) abundance and dysfunctional vasculature. Pan-cancer Matrix_barrier 164 PGF 38225927 Pan-cancer Pan-Cancer Matrix barrier Fibrogenic and vascular pericytes (PC) derived from FABP4+ progenitors were two distinct tumor-associated PC subpopulations that strongly interacted with PGF+ tips, resulting in excess extracellular matrix (ECM) abundance and dysfunctional vasculature. Pan-cancer Matrix_barrier 165 FN1 38043093 Ovarian cancer ovarian cancer Matrix barrier We observed that senescent mesothelia expressed an extracellular matrix with higher levels of fibronectin, laminins and hyaluronan than non-senescent controls. On senescent matrix, cancer cells adhered more efficiently, spread better, and moved faster and persistently, aiding the spread of cancer. Inhibition assays using RGD cyclopeptides suggested the adhesion was predominantly contributed by fibronectin and laminin Ovarian_cancer Matrix_barrier 166 HAS2 38043093 Ovarian cancer ovarian cancer Matrix barrier We observed that senescent mesothelia expressed an extracellular matrix with higher levels of fibronectin, laminins and hyaluronan than non-senescent controls. On senescent matrix, cancer cells adhered more efficiently, spread better, and moved faster and persistently, aiding the spread of cancer. Ovarian_cancer Matrix_barrier 167 MMP9 37984631 Breast cancer Breast cancer Matrix barrier Importantly, the generated ONOO- tripled the MMP-9 expression to induce ECM degradation, enabling much deeper penetration of Magnetic nanoparticles (MNPs) and benefiting magnetic hyperthermia therapy (MHT), chemodynamic therapy (CDT), and immunotherapy. Breast_cancer Matrix_barrier 168 BRD4 37968249 Pancreatic cancer pancreatic cancer Matrix barrier In pancreatic cancer, it is found that cancer-associated fibroblasts (CAFs) in the tumor microenvironment reduce the BET inhibitor JQ1 sensitivity by inducing BRD4 expression. Pancreatic_cancer Matrix_barrier 169 YAP1 37907483 Gastrointestinal cancer Intestinal carcinoma Matrix barrier Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP and a decrease in proliferation. Gastrointestinal_cancer Matrix_barrier 170 CD44 37866630 Breast cancer Breast cancer Matrix barrier Cell detachment from the extracellular matrix (ECM) triggers lipid raft disruption and anoikis, which is a barrier for cancer cells to metastasize. Compared to single circulating tumor cells (CTCs), our recent studies have demonstrated that CD44-mediatd cell aggregation enhances the stemness, survival and metastatic ability of aggregated cells. Breast_cancer Matrix_barrier 171 PSENEN 37866630 Breast cancer Breast cancer Matrix barrier CD44 and γ-secretase coexisted at lipid rafts in aggregated cells, which promoted CD44 cleavage and generated CD44 intracellular domain (CD44 ICD) to enhance stemness of aggregated cells. Breast_cancer Matrix_barrier 172 PDLIM7 37803433 Head and neck cancer nasopharyngeal carcinoma Matrix barrier Our current findings reveal the role of LMP1-stabilized peroxisome proliferator activated receptor coactivator-1a (PGC-1α) in anoikis resistance and immune escape to support the invasion and metastasis of NPC. Head_and_neck_cancer Matrix_barrier 173 PPARGC1A 37803433 Head and neck cancer nasopharyngeal carcinoma Matrix barrier Mechanistically, LMP1 enhances PGC-1α protein stability by promoting the interaction between arginine methyltransferase 1 (PRMT1) and PGC-1α to elevate the methylation modification of PGC-1α, thus endowing NPC cells with anoikis-resistance. Meanwhile, PGC-1α mediates the immune escape induced by LMP1 by coactivating with STAT3 to transcriptionally up-regulate PD-L1 expression. Head_and_neck_cancer Matrix_barrier 174 PRMT1 37803433 Head and neck cancer nasopharyngeal carcinoma Matrix barrier Mechanistically, LMP1 enhances PGC-1α protein stability by promoting the interaction between arginine methyltransferase 1 (PRMT1) and PGC-1α to elevate the methylation modification of PGC-1α, thus endowing NPC cells with anoikis-resistance. Meanwhile, PGC-1α mediates the immune escape induced by LMP1 by coactivating with STAT3 to transcriptionally up-regulate PD-L1 expression. Head_and_neck_cancer Matrix_barrier 175 STAT3 37803433 Head and neck cancer nasopharyngeal carcinoma Matrix barrier Mechanistically, LMP1 enhances PGC-1α protein stability by promoting the interaction between arginine methyltransferase 1 (PRMT1) and PGC-1α to elevate the methylation modification of PGC-1α, thus endowing NPC cells with anoikis-resistance. Meanwhile, PGC-1α mediates the immune escape induced by LMP1 by coactivating with STAT3 to transcriptionally up-regulate PD-L1 expression. Head_and_neck_cancer Matrix_barrier 176 SPINT1 37737895 Ovarian cancer ovarian cancer Matrix barrier We show that overactive matriptase, reflected in an increased ratio of matriptase to its inhibitor hepatocyte growth factor activator inhibitor 1 (HAI-1), disrupts cell-cell contacts to produce loose prometastatic spheroids that display increased mesothelial cell adhesion and submesothelial invasion. Ovarian_cancer Matrix_barrier 177 ST14 37737895 Ovarian cancer ovarian cancer Matrix barrier We show that overactive matriptase, reflected in an increased ratio of matriptase to its inhibitor hepatocyte growth factor activator inhibitor 1 (HAI-1), disrupts cell-cell contacts to produce loose prometastatic spheroids that display increased mesothelial cell adhesion and submesothelial invasion. Ovarian_cancer Matrix_barrier 178 F2RL1 37737895 Ovarian cancer ovarian cancer Matrix barrier We show that these activities are dependent on the matriptase activation of a protease-activated receptor-2 (PAR-2) signaling pathway involving PI3K/Akt and MMP9-induced disruption of cell-cell adhesion by the release of the soluble E-cadherin ectodomain. Ovarian_cancer Matrix_barrier 179 AKT1 37737895 Ovarian cancer ovarian cancer Matrix barrier We show that these activities are dependent on the matriptase activation of a protease-activated receptor-2 (PAR-2) signaling pathway involving PI3K/Akt and MMP9-induced disruption of cell-cell adhesion by the release of the soluble E-cadherin ectodomain. Ovarian_cancer Matrix_barrier 180 MMP9 37737895 Ovarian cancer ovarian cancer Matrix barrier We show that these activities are dependent on the matriptase activation of a protease-activated receptor-2 (PAR-2) signaling pathway involving PI3K/Akt and MMP9-induced disruption of cell-cell adhesion by the release of the soluble E-cadherin ectodomain. Ovarian_cancer Matrix_barrier 181 ITGB1 37729438 Other cancers adenoid cystic carcinoma Matrix barrier Given the key roles of cancer associated fibroblasts (CAFs) in shaping tumor stroma, this study shows a CAF-associated ITGB1-inactivating peptide-enriched membrane nanodelivery system (designated as PMNPs-D) to simultaneously target CAFs and tumor cells for boosted chemotherapy through promoted drug perfusion. Other_cancers Matrix_barrier 182 FAP 37729438 Other cancers adenoid cystic carcinoma Matrix barrier After prolonged blood circulation and actively targeting in tumor sites, PMNPs-D can respond to CAF-overexpressed fibroblast activation protein-α (FAP-α) to trigger the release of FNIII14, which will bind to ITGB1 and inhibit CAFs' biological function in producing the stromal matrix, thereby loosening the condensed stromal structure and enhancing the permeability of nanotherapeutics in tumors. Other_cancers Matrix_barrier 183 SDC1 37652015 Liver cancer hepatocellular carcinoma Matrix barrier Serum SDC1 levels are high in patients with HCC with disease progression and recurrence. The expression of pro-angiogenic factors VEGF and fibroblast growthfactor 2 (FGF-2) was reduced in thioacetamide-induced ratsthrough the inhibition of SDC1, a finding suggestive of its role inangiogenesis and HCC progression. Liver_cancer Matrix_barrier 184 SDC1 21224069 Liver cancer hepatocellular carcinoma Matrix barrier SDC1 expressed by humanmammary fibroblasts, in association with integrin, promoted the assembly of ECM fibers in parallel arrays, which increased migration and invasion of breast cancer cells. Liver_cancer Matrix_barrier 185 GPC3 21224069 Liver cancer hepatocellular carcinoma Matrix barrier GPC3 stimulates Wnt signaling and the insulin-like growth factor (IGF) and promotes EMT via extracellular signal-regulated kinase (ERK) signaling. Liver_cancer Matrix_barrier 186 IGF1 21224069 Liver cancer hepatocellular carcinoma Matrix barrier GPC3 stimulates Wnt signaling and the insulin-like growth factor (IGF) and promotes EMT via extracellular signal-regulated kinase (ERK) signaling. Liver_cancer Matrix_barrier 187 AGRN 21224069 Liver cancer hepatocellular carcinoma Matrix barrier Agrin promotes HCC cell proliferation, migration, and invasiveness, and supplementation with a recombinant soluble agrin (sAgrin) readily revives cancer cell proliferation and migration defects caused by the genetic ablation of agrin. Liver_cancer Matrix_barrier 188 YAP1 21224069 Liver cancer hepatocellular carcinoma Matrix barrier Besides serving as major oncogenic factors that promote liver fibrosis and HCC by engaging transcriptional enhanced associate domain (TEAD) transcriptional factors, YAP/TAZ are widely regarded as mechanosensors that respond to a variety of extrinsic physical stimuli. Liver_cancer Matrix_barrier 189 WWTR1 21224069 Liver cancer hepatocellular carcinoma Matrix barrier Besides serving as major oncogenic factors that promote liver fibrosis and HCC by engaging transcriptional enhanced associate domain (TEAD) transcriptional factors, YAP/TAZ are widely regarded as mechanosensors that respond to a variety of extrinsic physical stimuli. Liver_cancer Matrix_barrier 190 KDR 21224069 Liver cancer hepatocellular carcinoma Matrix barrier Agrin in the TME recruits endothelial cells (ECs) and controls their angiogenic properties.79,80 It promotes angiogenesis by increasing VEGF receptor 2 (VEGFR2) stability in a matrix stiffness-sensed fashion Liver_cancer Matrix_barrier 191 TNC 21224069 Liver cancer hepatocellular carcinoma Matrix barrier The overexpression of TNCN in HCC is associated with a poor prognosis. Further, TNF-a derived from the inflammatory TME upregulates TNCN expression in HCC cells and in turn enhances migration through the WNT/b-catenin pathway. Liver_cancer Matrix_barrier 192 TNF 21224069 Liver cancer hepatocellular carcinoma Matrix barrier The overexpression of TNCN in HCC is associated with a poor prognosis. Further, TNF-a derived from the inflammatory TME upregulates TNCN expression in HCC cells and in turn enhances migration through the WNT/b-catenin pathway. Liver_cancer Matrix_barrier 193 SPP1 21224069 Liver cancer hepatocellular carcinoma Matrix barrier OPN is associated with tumor grade, tumor size, and recurrence of HCC.99,100 It binds to CD44 and integrin receptor avb3 and induces proliferation, infiltration, metastasis, and tumor progression through mitogen-activated protein kinases (MAPKs), nuclear factor kB (NF-kB), and the PIK3/AKTpathway. Liver_cancer Matrix_barrier 194 CXCL12 37572982 Pancreatic cancer pancreatic ductal adenocarcinoma Matrix barrier Specifically, a nanodrug incorporating calcipotriol and anti-CXCL12 siRNA was synthesized to synchronously inactivate matrix-producing pancreatic stellate cells and suppress the infiltration of regulatory T cells. Pancreatic_cancer Matrix_barrier 195 TGFB1 37480223 Pancreatic cancer pancreatic cancer Matrix barrier Controls desmoplastic reaction and fibrosis, promotes the production of collagen, increases the production of extracellular matrix proteins, and regulates immune response and inflammatory processes. Pancreatic_cancer Matrix_barrier 196 HGF 37480223 Pancreatic cancer pancreatic cancer Matrix barrier Induces the production of extracellular matrix molecules and collagen, leading to the formation of desmoplastic reaction and fibrosis. Pancreatic_cancer Matrix_barrier 197 IL1A 37480223 Pancreatic cancer pancreatic cancer Matrix barrier IL1 induces fibrosis in various cell types and is important in the development of desmoplastic reaction and fibrosis. Pancreatic_cancer Matrix_barrier 198 IL1B 37480223 Pancreatic cancer pancreatic cancer Matrix barrier IL1 induces fibrosis in various cell types and is important in the development of desmoplastic reaction and fibrosis. Pancreatic_cancer Matrix_barrier 199 TNF 37480223 Pancreatic cancer pancreatic cancer Matrix barrier Promotes the production of extracellular matrix components, cell proliferation, and cell migration, contributing to the development of desmoplastic reaction. Pancreatic_cancer Matrix_barrier 200 HDAC9 37480223 Pancreatic cancer pancreatic cancer Matrix barrier Involved in the regulation of gene expression, production of extracellular matrix proteins, and tissue structure remodeling. HDAC inhibitors are studied as potential therapy for desmoplastic reaction and fibrosis. Pancreatic_cancer Matrix_barrier 201 HIF1A 37480223 Pancreatic cancer pancreatic cancer Matrix barrier Transcription factor involved in regulation of genes related to desmoplastic reaction and fibrosis. Modulates the production of collagen, extracellular matrix proteins, and other regulators of wound healing. Also regulates proinflammatory cytokines, chemokines, and adhesion molecules and interacts with viral oncogenes that promote the development of advanced cervical cancer. Pancreatic_cancer Matrix_barrier 202 NFKB1 37480223 Pancreatic cancer pancreatic cancer Matrix barrier Important regulator of desmoplastic reaction and fibrosis. Activation leads to increased inflammation, fibroblast proliferation, and extracellular matrix deposition. Regulates multiple inflammatory pathways including production of cytokines, chemokines, and growth factors. Also regulates expression of genes involved in the regulation of desmoplastic response. Pancreatic_cancer Matrix_barrier 203 TGFB1 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier CAFs can also produce many growth factors and proinflammatory cytokines, notably, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and CXC-chemokine ligand (CXCL12), to promote angiogenesis and recruit immunosuppressive cells into the TME to assist in immune evasion. Pancreatic_cancer Matrix_barrier 204 VEGFA 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier CAFs can also produce many growth factors and proinflammatory cytokines, notably, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and CXC-chemokine ligand (CXCL12), to promote angiogenesis and recruit immunosuppressive cells into the TME to assist in immune evasion. Pancreatic_cancer Matrix_barrier 205 IL6 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier CAFs can also produce many growth factors and proinflammatory cytokines, notably, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and CXC-chemokine ligand (CXCL12), to promote angiogenesis and recruit immunosuppressive cells into the TME to assist in immune evasion. Pancreatic_cancer Matrix_barrier 206 CXCL12 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier CAFs can also produce many growth factors and proinflammatory cytokines, notably, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and CXC-chemokine ligand (CXCL12), to promote angiogenesis and recruit immunosuppressive cells into the TME to assist in immune evasion. Pancreatic_cancer Matrix_barrier 207 PDCD1LG2 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier Some CAFs subpopulations express programmed cell death 1 ligand 1/2 (PD-L1/2), a target for immune checkpoint inhibitor. Pancreatic_cancer Matrix_barrier 208 CD274 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier Some CAFs subpopulations express programmed cell death 1 ligand 1/2 (PD-L1/2), a target for immune checkpoint inhibitor. Pancreatic_cancer Matrix_barrier 209 ABL2 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier Metabolites or metabolic enzymes, such as indoleamine-2,3-dioxygenase (IDO), arginase (Arg), adenosine, and tryoptase produced by certain subtypes of CAFs favor the recruitment and differentiation of regulatory T cell (Tregs), mast cells, and tumor-associated macrophages (TAMs). Pancreatic_cancer Matrix_barrier 210 IDO1 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier Metabolites or metabolic enzymes, such as indoleamine-2,3-dioxygenase (IDO), arginase (Arg), adenosine, and tryoptase produced by certain subtypes of CAFs favor the recruitment and differentiation of regulatory T cell (Tregs), mast cells, and tumor-associated macrophages (TAMs). Pancreatic_cancer Matrix_barrier 211 MMP9 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier CAFs can synthesize the extracellular matrix (ECM) components such as collagen, fibronectin, and matrix metalloproteinases (MMPs). Multiple CAF subtypes contribute to increased ECM stiffness, which in turn reduces the infiltration of effector T cells. Pancreatic_cancer Matrix_barrier 212 MMP2 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier CAFs can synthesize the extracellular matrix (ECM) components such as collagen, fibronectin, and matrix metalloproteinases (MMPs). Multiple CAF subtypes contribute to increased ECM stiffness, which in turn reduces the infiltration of effector T cells. Pancreatic_cancer Matrix_barrier 213 CXCL12 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier Targeting the important signals and effectors of CAFs, such as CX-chemokine ligand 12-CX chemokine receptor 4 (CXCL12-CXCR4) interaction, Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway, transforming growth factor-β (TGF-β), and Hedgehog signaling pathway, can be used to inhibit the function of CAFs. Pancreatic_cancer Matrix_barrier 214 CXCR4 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier Targeting the important signals and effectors of CAFs, such as CX-chemokine ligand 12-CX chemokine receptor 4 (CXCL12-CXCR4) interaction, Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway, transforming growth factor-β (TGF-β), and Hedgehog signaling pathway, can be used to inhibit the function of CAFs. Pancreatic_cancer Matrix_barrier 215 JAK2 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier Targeting the important signals and effectors of CAFs, such as CX-chemokine ligand 12-CX chemokine receptor 4 (CXCL12-CXCR4) interaction, Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway, transforming growth factor-β (TGF-β), and Hedgehog signaling pathway, can be used to inhibit the function of CAFs. Pancreatic_cancer Matrix_barrier 216 STAT3 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier Targeting the important signals and effectors of CAFs, such as CX-chemokine ligand 12-CX chemokine receptor 4 (CXCL12-CXCR4) interaction, Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway, transforming growth factor-β (TGF-β), and Hedgehog signaling pathway, can be used to inhibit the function of CAFs. Pancreatic_cancer Matrix_barrier 217 TGFB1 31462327 Pancreatic cancer pancreatic adenocarcinoma Matrix barrier Targeting the important signals and effectors of CAFs, such as CX-chemokine ligand 12-CX chemokine receptor 4 (CXCL12-CXCR4) interaction, Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway, transforming growth factor-β (TGF-β), and Hedgehog signaling pathway, can be used to inhibit the function of CAFs. Pancreatic_cancer Matrix_barrier 218 COL6A1 37331435 Prostate cancer prostate tumor Matrix barrier Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. Prostate_cancer Matrix_barrier 219 COL6A3 37331435 Prostate cancer prostate tumor Matrix barrier Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. Prostate_cancer Matrix_barrier 220 COL6A2 37331435 Prostate cancer prostate tumor Matrix barrier Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. Prostate_cancer Matrix_barrier 221 COL6A5 37331435 Prostate cancer prostate tumor Matrix barrier Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. Prostate_cancer Matrix_barrier 222 COL6A6 37331435 Prostate cancer prostate tumor Matrix barrier Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. Prostate_cancer Matrix_barrier 223 CD4 37331435 Prostate cancer prostate tumor Matrix barrier Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. Prostate_cancer Matrix_barrier 224 ITGB4 37331435 Prostate cancer prostate tumor Matrix barrier Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. Prostate_cancer Matrix_barrier 225 ITGB3 37331435 Prostate cancer prostate tumor Matrix barrier Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. Prostate_cancer Matrix_barrier 226 ITGB1 37331435 Prostate cancer prostate tumor Matrix barrier Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin β1 clustering. Prostate_cancer Matrix_barrier 227 ITGA1 37331435 Prostate cancer prostate tumor Matrix barrier We found that CD4+ T cells largely lack expression of integrin α1 in the prostate tumor microenvironment and that blockade of α1β1 integrin heterodimers inhibited CD8+ T cell motility on prostate fibroblast-derived matrix, while re-expression of ITGA1 improved motility. Prostate_cancer Matrix_barrier 228 ITGA2 37331435 Prostate cancer prostate tumor Matrix barrier We found that CD4+ T cells largely lack expression of integrin α1 in the prostate tumor microenvironment and that blockade of α1β1 integrin heterodimers inhibited CD8+ T cell motility on prostate fibroblast-derived matrix, while re-expression of ITGA1 improved motility. Prostate_cancer Matrix_barrier 229 ITGA4 37331435 Prostate cancer prostate tumor Matrix barrier We found that CD4+ T cells largely lack expression of integrin α1 in the prostate tumor microenvironment and that blockade of α1β1 integrin heterodimers inhibited CD8+ T cell motility on prostate fibroblast-derived matrix, while re-expression of ITGA1 improved motility. Prostate_cancer Matrix_barrier 230 CD8A 37331435 Prostate cancer prostate tumor Matrix barrier We found that CD4+ T cells largely lack expression of integrin α1 in the prostate tumor microenvironment and that blockade of α1β1 integrin heterodimers inhibited CD8+ T cell motility on prostate fibroblast-derived matrix, while re-expression of ITGA1 improved motility. Prostate_cancer Matrix_barrier 231 DDR1 37328286 Breast cancer breast cancer Matrix barrier PRTH-101 inhibited DDR1 phosphorylation, decreased collagen-mediated cell attachment, and significantly blocked DDR1 shedding from the cell surface. Treatment of tumor-bearing mice with PRTH-101 in vivo disrupted collagen fiber alignment (a physical barrier) in the tumor extracellular matrix (ECM) and enhanced CD8+ T cell infiltration in tumors. Breast_cancer Matrix_barrier 232 YAP1 37185904 Pan-cancer pan-cancer Matrix barrier We report that the knockdown of YAP and TAZ or their inhibition by verteporfin induces a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Pan-cancer Matrix_barrier 233 WWTR1 37185904 Pan-cancer pan-cancer Matrix barrier We report that the knockdown of YAP and TAZ or their inhibition by verteporfin induces a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Pan-cancer Matrix_barrier 234 SH3PXD2A 37185904 Pan-cancer pan-cancer Matrix barrier Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Pan-cancer Matrix_barrier 235 MMP14 37185904 Pan-cancer pan-cancer Matrix barrier Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Pan-cancer Matrix_barrier 236 ABCB1 37174021 Other cancers chondrosarcoma Matrix barrier Hypovascularization, extracellular matrix composition of collagen, proteoglycans, and hyaluronan create a mechanical barrier for tumor suppressive immune cells. Comparatively low proliferation rates, MDR-1 expression and an acidic tumor microenvironment further limit therapeutic options in Chondrosarcoma (CHS). Other_cancers Matrix_barrier 237 NQO1 37099721 Breast cancer Breast Cancer Matrix barrier Based on overexpressed NAD(P)H quinone oxidoreductase 1 (NQO1) in breast cancer, a TME-responsive drug (NQO1-SN38) is designed and it is combined with the inhibitor (i.e., β-Aminopropionitrile, BAPN) for Lysyl oxidases (Lox) that contributes to the tumor stiffness, for mechanochemical therapy. It is demonstrated that NQO1 can trigger the degradation of NQO1-SN38 and release SN38, showing nearly twice tumor inhibition efficiency compared with SN38 treatment in vitro. Lox inhibition with BAPN significantly reduces collagen deposition and enhances drug penetration in tumor heterospheroids in vitro. Breast_cancer Matrix_barrier 238 LOX 37099721 Breast cancer Breast Cancer Matrix barrier Based on overexpressed NAD(P)H quinone oxidoreductase 1 (NQO1) in breast cancer, a TME-responsive drug (NQO1-SN38) is designed and it is combined with the inhibitor (i.e., β-Aminopropionitrile, BAPN) for Lysyl oxidases (Lox) that contributes to the tumor stiffness, for mechanochemical therapy. It is demonstrated that NQO1 can trigger the degradation of NQO1-SN38 and release SN38, showing nearly twice tumor inhibition efficiency compared with SN38 treatment in vitro. Lox inhibition with BAPN significantly reduces collagen deposition and enhances drug penetration in tumor heterospheroids in vitro. Breast_cancer Matrix_barrier 239 MMP2 37083874 Breast cancer breast cancer Matrix barrier Upon arrival at the tumor microenvironment (TME), the small satellite micelle encapsulating ET was detached from the core micelle in response to MMP-2, which not only drained to TDLNs via tumor-draining lymphatic vessels and inhibited the FAO of metastatic tumor cells, but also blocked M2-like macrophage polarization in the TME. Breast_cancer Matrix_barrier 240 ACTA2 32748119 Pancreatic cancer pancreatic cancer Matrix barrier To date there has been two major CAF subtypes reported which includes myofibroblastic CAFs (myCAFs), these express a high level of α-smooth muscle actin (αSMA) and reside closely to the tumour and inflammatory CAFs (iCAFs) which express lower levels of αSMA but high levels of chemokines and cytokines and locate more distally from the tumour. Pancreatic_cancer Matrix_barrier 241 ACTA1 32748119 Pancreatic cancer pancreatic cancer Matrix barrier To date there has been two major CAF subtypes reported which includes myofibroblastic CAFs (myCAFs), these express a high level of α-smooth muscle actin (αSMA) and reside closely to the tumour and inflammatory CAFs (iCAFs) which express lower levels of αSMA but high levels of chemokines and cytokines and locate more distally from the tumour. Pancreatic_cancer Matrix_barrier 242 HLA-DRB1 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 243 HLA-DQB1 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 244 HLA-DQA1 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 245 HLA-DRA 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 246 HLA-DQA2 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 247 HLA-DRB5 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 248 HLA-DPB1 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 249 HLA-DPA1 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 250 HLA-DRB3 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 251 HLA-DRB4 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 252 HLA-DMB 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 253 HLA-DOA 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 254 HLA-DOB 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 255 HLA-DMA 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 256 HLA-DQB2 32748119 Pancreatic cancer pancreatic cancer Matrix barrier Recently a third subtype of CAF has been identified and this subset which they classify as antigen-presenting CAFs (apCAFs) expresses MHC class II-related genes to CD4+ T cells and modulates the immune axis capacity. Pancreatic_cancer Matrix_barrier 257 CCL2 28302482 Colon cancer colorectal cancer Matrix barrier Mechanistically, CAFs with high FAP expression promoted immunosuppression in the CRC tumor immune microenvironment by up-regulating CCL2 secretion, recruiting myeloid cells, and decreasing T-cell activity. Colon_cancer Matrix_barrier 258 CXCL1 29136508 Lung cancer non-small cell lung cancer, breast cancer, and colon adenocarcinoma. Matrix barrier We found that FAP-CAR-T cell induced depletion of CAF was associated with significant reduction in Cxcl1 mRNA in tumors and a significant decrease in the presence of PMN-MDSC. Lung_cancer Matrix_barrier 259 CXCL1 29136508 Breast cancer non-small cell lung cancer, breast cancer, and colon adenocarcinoma. Matrix barrier We found that FAP-CAR-T cell induced depletion of CAF was associated with significant reduction in Cxcl1 mRNA in tumors and a significant decrease in the presence of PMN-MDSC. Breast_cancer Matrix_barrier 260 CXCL1 29136508 Colon cancer non-small cell lung cancer, breast cancer, and colon adenocarcinoma. Matrix barrier We found that FAP-CAR-T cell induced depletion of CAF was associated with significant reduction in Cxcl1 mRNA in tumors and a significant decrease in the presence of PMN-MDSC. Colon_cancer Matrix_barrier 261 CXCR2 36480035 Pan-cancer review, pan-cancer Matrix barrier Selective inhibition of CXCR2 might be an interesting option since this receptor is highly expressed in CAFs and CXCL1-CXCR2 signalling controls the expression of numerous cytokines involved in the recruitment of neutrophils. Pan-cancer Matrix_barrier 262 IL6 27593937 Liver cancer hepatic carcinoma Matrix barrier Tumor-associated fibroblasts (TAFs) attracted monocytes by the stromal cell-derived factor (SDF)-1a/CXCR4 pathway and induced their differentiation into MDSCs through interleukin (IL)-6-mediated STAT3 activation. Liver_cancer Matrix_barrier 263 TGFB1 32213632 Melanoma melanoma, breast cancer, and bladder cancer Matrix barrier Specific targeting of TGFβ1, a molecule secreted by myCAFs, was also effective in tumors expressing more than one TGFβ isoform. Combined SRK-181-mIgG1 and anti-PD-1 treatment resulted in increased intratumoral CD8+ T cells and decreased immunosuppressive myeloid cells. Melanoma Matrix_barrier 264 TGFB1 32213632 Breast cancer melanoma, breast cancer, and bladder cancer Matrix barrier Specific targeting of TGFβ1, a molecule secreted by myCAFs, was also effective in tumors expressing more than one TGFβ isoform. Combined SRK-181-mIgG1 and anti-PD-1 treatment resulted in increased intratumoral CD8+ T cells and decreased immunosuppressive myeloid cells. Breast_cancer Matrix_barrier 265 TGFB1 32213632 Bladder cancer melanoma, breast cancer, and bladder cancer Matrix barrier Specific targeting of TGFβ1, a molecule secreted by myCAFs, was also effective in tumors expressing more than one TGFβ isoform. Combined SRK-181-mIgG1 and anti-PD-1 treatment resulted in increased intratumoral CD8+ T cells and decreased immunosuppressive myeloid cells. Bladder_cancer Matrix_barrier 266 COX2 35908547 Lung cancer Lung cancer Matrix barrier Here, by single-cell RNA sequencing and immunofluorescence, we identified a population of cyclooxygenase 2 (COX-2)-expressing adventitial fibroblasts that remodeled the lung immune microenvironment. Genetic ablation of Ptgs2 (encoding COX-2) in fibroblasts was sufficient to reverse the immune-suppressive phenotypes of lung-resident myeloid cells, resulting in heightened immune activation and diminished lung metastasis in multiple breast cancer models. Lung_cancer Matrix_barrier 267 IL1B 35908547 Lung cancer Lung cancer Matrix barrier At steady-state, fibroblasts in the lungs produced prostaglandin E2 (PGE2), which drove dysfunctional dendritic cells (DCs) and suppressive monocytes. This lung-intrinsic stromal program was propagated by tumor-associated inflammation, particularly the pro-inflammatory cytokine interleukin-1β, supporting a pre-metastatic niche. Lung_cancer Matrix_barrier 268 PTGES2 35908547 Lung cancer Lung cancer Matrix barrier At steady-state, fibroblasts in the lungs produced prostaglandin E2 (PGE2), which drove dysfunctional dendritic cells (DCs) and suppressive monocytes. This lung-intrinsic stromal program was propagated by tumor-associated inflammation, particularly the pro-inflammatory cytokine interleukin-1β, supporting a pre-metastatic niche. Lung_cancer Matrix_barrier 269 ARG1 35908547 Lung cancer Lung cancer Matrix barrier In addition, the expression levels of multiple immunosuppression-associated genes, including Arg1, Cd274, Il10, Nos2, Ptgs2, and Pdcd1lg2, were increased in BM-DCs upon stimulation by wild type (WT) lung fibroblasts. Lung_cancer Matrix_barrier 270 CD274 35908547 Lung cancer Lung cancer Matrix barrier In addition, the expression levels of multiple immunosuppression-associated genes, including Arg1, Cd274, Il10, Nos2, Ptgs2, and Pdcd1lg2, were increased in BM-DCs upon stimulation by wild type (WT) lung fibroblasts. Lung_cancer Matrix_barrier 271 TSC22D1 35908547 Lung cancer Lung cancer Matrix barrier In addition, the expression levels of multiple immunosuppression-associated genes, including Arg1, Cd274, Il10, Nos2, Ptgs2, and Pdcd1lg2, were increased in BM-DCs upon stimulation by wild type (WT) lung fibroblasts. Lung_cancer Matrix_barrier 272 NOS2 35908547 Lung cancer Lung cancer Matrix barrier In addition, the expression levels of multiple immunosuppression-associated genes, including Arg1, Cd274, Il10, Nos2, Ptgs2, and Pdcd1lg2, were increased in BM-DCs upon stimulation by wild type (WT) lung fibroblasts. Lung_cancer Matrix_barrier 273 IL10 35908547 Lung cancer Lung cancer Matrix barrier In addition, the expression levels of multiple immunosuppression-associated genes, including Arg1, Cd274, Il10, Nos2, Ptgs2, and Pdcd1lg2, were increased in BM-DCs upon stimulation by wild type (WT) lung fibroblasts. Lung_cancer Matrix_barrier 274 FOXP3 29455927 Breast cancer breast cancer Matrix barrier By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25HighFOXP3High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. Breast_cancer Matrix_barrier 275 IL2RA 29455927 Breast cancer breast cancer Matrix barrier By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25HighFOXP3High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. Breast_cancer Matrix_barrier 276 NT5E 29455927 Breast cancer breast cancer Matrix barrier By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25HighFOXP3High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. Breast_cancer Matrix_barrier 277 DPP4 29455927 Breast cancer breast cancer Matrix barrier By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25HighFOXP3High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. Breast_cancer Matrix_barrier 278 CD276 29455927 Breast cancer breast cancer Matrix barrier By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25HighFOXP3High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. Breast_cancer Matrix_barrier 279 IL12B 29455927 Breast cancer breast Cancer Matrix barrier Another CAF subtype that has been shown to control Treg differentiation and promote their expansion in the TME is the apCAFs. These mesothelial-derived cells, whose differentiation has been attributed to several factors (IL-12, IFN-γ, IL-1β, and TGFβ), are characterised by the expression of MHC-class II molecules but lack expression of traditional co-stimulatory proteins (e.g. CD80, CD86, and CD40)  Breast_cancer Matrix_barrier 280 IFNG 36480035 Pan-cancer review, pan-cancer Matrix barrier Another CAF subtype that has been shown to control Treg differentiation and promote their expansion in the TME is the apCAFs. These mesothelial-derived cells, whose differentiation has been attributed to several factors (IL-12, IFN-γ, IL-1β, and TGFβ), are characterised by the expression of MHC-class II molecules but lack expression of traditional co-stimulatory proteins (e.g. CD80, CD86, and CD40)  Pan-cancer Matrix_barrier 281 CD80 36480035 Pan-cancer review, pan-cancer Matrix barrier Another CAF subtype that has been shown to control Treg differentiation and promote their expansion in the TME is the apCAFs. These mesothelial-derived cells, whose differentiation has been attributed to several factors (IL-12, IFN-γ, IL-1β, and TGFβ), are characterised by the expression of MHC-class II molecules but lack expression of traditional co-stimulatory proteins (e.g. CD80, CD86, and CD40)  Pan-cancer Matrix_barrier 282 CD86 36480035 Pan-cancer review, pan-cancer Matrix barrier Another CAF subtype that has been shown to control Treg differentiation and promote their expansion in the TME is the apCAFs. These mesothelial-derived cells, whose differentiation has been attributed to several factors (IL-12, IFN-γ, IL-1β, and TGFβ), are characterised by the expression of MHC-class II molecules but lack expression of traditional co-stimulatory proteins (e.g. CD80, CD86, and CD40)  Pan-cancer Matrix_barrier 283 CD40 36480035 Pan-cancer review, pan-cancer Matrix barrier Another CAF subtype that has been shown to control Treg differentiation and promote their expansion in the TME is the apCAFs. These mesothelial-derived cells, whose differentiation has been attributed to several factors (IL-12, IFN-γ, IL-1β, and TGFβ), are characterised by the expression of MHC-class II molecules but lack expression of traditional co-stimulatory proteins (e.g. CD80, CD86, and CD40)  Pan-cancer Matrix_barrier 284 CD274 30873585 Melanoma melanoma and colorectal carcinoma Matrix barrier Herein, by scrutinizing the expression of α-SMA and PD-L1 in melanoma and CRC tissues, we found that CAFs was positive correlated with PD-L1 expression. Further analyses showed that CAFs promoted PD-L1 expression in mice tumor cells. Melanoma Matrix_barrier 285 CD274 30873585 Colon cancer melanoma and colorectal carcinoma Matrix barrier Herein, by scrutinizing the expression of α-SMA and PD-L1 in melanoma and CRC tissues, we found that CAFs was positive correlated with PD-L1 expression. Further analyses showed that CAFs promoted PD-L1 expression in mice tumor cells. Colon_cancer Matrix_barrier 286 PIK3CD 30873585 Melanoma melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Melanoma Matrix_barrier 287 PIK3CD 30873585 Colon cancer melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Colon_cancer Matrix_barrier 288 PIK3CG 30873585 Melanoma melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Melanoma Matrix_barrier 289 PIK3CG 30873585 Colon cancer melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Colon_cancer Matrix_barrier 290 PIK3CA 30873585 Melanoma melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Melanoma Matrix_barrier 291 PIK3CA 30873585 Colon cancer melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Colon_cancer Matrix_barrier 292 PIK3CB 30873585 Melanoma melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Melanoma Matrix_barrier 293 PIK3CB 30873585 Colon cancer melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Colon_cancer Matrix_barrier 294 CXCL5 30873585 Melanoma melanoma and colorectal carcinoma Matrix barrier By detecting a majority of cytokines expression in normal mice fibroblasts and CAFs, we determined that CXCL5 was abnormal high expression in CAFs and the immunohistochemistry and in situ hybridization confirmed that were CAFs which were expressing CXCL5. Melanoma Matrix_barrier 295 CXCL5 30873585 Colon cancer melanoma and colorectal carcinoma Matrix barrier By detecting a majority of cytokines expression in normal mice fibroblasts and CAFs, we determined that CXCL5 was abnormal high expression in CAFs and the immunohistochemistry and in situ hybridization confirmed that were CAFs which were expressing CXCL5. Colon_cancer Matrix_barrier 296 AKT1 30873585 Melanoma melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Melanoma Matrix_barrier 297 AKT1 30873585 Colon cancer melanoma and colorectal carcinoma Matrix barrier Functionally, CXCL5 derived by CAFs promoted PD-L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD-L1 expression via PI3K/AKT signaling. Colon_cancer Matrix_barrier 298 FAS 29507342 Lung cancer lung adenocarcinoma and melanoma Matrix barrier We provide evidence of direct interactions between stroma and T cells driving suppression, showing that cancer-associated fibroblasts (CAFs) sample, process and cross-present antigen, killing CD8+ T cells in an antigen-specific, antigen-dependent manner via PD-L2 and FASL. Inhibitory ligand expression is observed in CAFs from human tumours, and neutralisation of PD-L2 or FASL reactivates T cell cytotoxic capacity in vitro and in vivo. Lung_cancer Matrix_barrier 299 FAS 29507342 Melanoma lung adenocarcinoma and melanoma Matrix barrier We provide evidence of direct interactions between stroma and T cells driving suppression, showing that cancer-associated fibroblasts (CAFs) sample, process and cross-present antigen, killing CD8+ T cells in an antigen-specific, antigen-dependent manner via PD-L2 and FASL. Inhibitory ligand expression is observed in CAFs from human tumours, and neutralisation of PD-L2 or FASL reactivates T cell cytotoxic capacity in vitro and in vivo. Melanoma Matrix_barrier 300 PDCD1LG2 29507342 Lung cancer lung adenocarcinoma and melanoma Matrix barrier We provide evidence of direct interactions between stroma and T cells driving suppression, showing that cancer-associated fibroblasts (CAFs) sample, process and cross-present antigen, killing CD8+ T cells in an antigen-specific, antigen-dependent manner via PD-L2 and FASL. Inhibitory ligand expression is observed in CAFs from human tumours, and neutralisation of PD-L2 or FASL reactivates T cell cytotoxic capacity in vitro and in vivo. Lung_cancer Matrix_barrier 301 PDCD1LG2 29507342 Melanoma lung adenocarcinoma and melanoma Matrix barrier We provide evidence of direct interactions between stroma and T cells driving suppression, showing that cancer-associated fibroblasts (CAFs) sample, process and cross-present antigen, killing CD8+ T cells in an antigen-specific, antigen-dependent manner via PD-L2 and FASL. Inhibitory ligand expression is observed in CAFs from human tumours, and neutralisation of PD-L2 or FASL reactivates T cell cytotoxic capacity in vitro and in vivo. Melanoma Matrix_barrier 302 LAG3 35264435 Colon cancer colorectal cancer Matrix barrier Cognate interaction between CD8+ T cells and cross-presenting CAFs suppressed T cell function, reflected by decreased cytotoxicity, reduced activation (CD137) and increased exhaustion (TIM3, LAG3 and CD39) marker expression. Colon_cancer Matrix_barrier 303 HAVCR2 35264435 Colon cancer colorectal cancer Matrix barrier Cognate interaction between CD8+ T cells and cross-presenting CAFs suppressed T cell function, reflected by decreased cytotoxicity, reduced activation (CD137) and increased exhaustion (TIM3, LAG3 and CD39) marker expression. Colon_cancer Matrix_barrier 304 PDPN 36480035 Pan-cancer review, pan-cancer Matrix barrier Interestingly, in chronic inflammation, PDPN+/FAP+ fibroblasts are essential in the formation of these structures through a multistep process involving the secretion of numerous cytokines and chemokines (e.g. IL13, CXCL13, CCL19, and CCL21), and they also drive pathology  Pan-cancer Matrix_barrier 305 FAP 36480035 Pan-cancer review, pan-cancer Matrix barrier Interestingly, in chronic inflammation, PDPN+/FAP+ fibroblasts are essential in the formation of these structures through a multistep process involving the secretion of numerous cytokines and chemokines (e.g. IL13, CXCL13, CCL19, and CCL21), and they also drive pathology  Pan-cancer Matrix_barrier 306 IL13 36480035 Pan-cancer review, pan-cancer Matrix barrier Interestingly, in chronic inflammation, PDPN+/FAP+ fibroblasts are essential in the formation of these structures through a multistep process involving the secretion of numerous cytokines and chemokines (e.g. IL13, CXCL13, CCL19, and CCL21), and they also drive pathology  Pan-cancer Matrix_barrier 307 CXCL13 36480035 Pan-cancer review, pan-cancer Matrix barrier Interestingly, in chronic inflammation, PDPN+/FAP+ fibroblasts are essential in the formation of these structures through a multistep process involving the secretion of numerous cytokines and chemokines (e.g. IL13, CXCL13, CCL19, and CCL21), and they also drive pathology  Pan-cancer Matrix_barrier 308 CCL19 36480035 Pan-cancer review, pan-cancer Matrix barrier Interestingly, in chronic inflammation, PDPN+/FAP+ fibroblasts are essential in the formation of these structures through a multistep process involving the secretion of numerous cytokines and chemokines (e.g. IL13, CXCL13, CCL19, and CCL21), and they also drive pathology  Pan-cancer Matrix_barrier 309 CCL21 36480035 Pan-cancer review, pan-cancer Matrix barrier Interestingly, in chronic inflammation, PDPN+/FAP+ fibroblasts are essential in the formation of these structures through a multistep process involving the secretion of numerous cytokines and chemokines (e.g. IL13, CXCL13, CCL19, and CCL21), and they also drive pathology  Pan-cancer Matrix_barrier 310 ACTA2 28232471 Pancreatic cancer pancreatic cancer Matrix barrier Upon activation, PSCs express the myofibroblast protein α-smooth muscle actin (αSMA, gene name Acta2) and secrete factors that stimulate tumor growth, cell survival, and metastasis. Pancreatic_cancer Matrix_barrier 311 FAP 28232471 Pancreatic cancer pancreatic cancer Matrix barrier Immunofluorescence analysis of FAP, a PSC marker, and αSMA expression in human PDA tissues revealed that the majority of fibroblasts expressed FAP and low levels of αSMA, whereas a subpopulation of FAP+ cells showed substantially elevated expression levels of αSMA. These FAP+ αSMAhigh cells could also be delineated by RNA in situ hybridization (ISH), and were located in direct proximity to neoplastic cells, forming a periglandular ring surrounding cancer cell clusters Pancreatic_cancer Matrix_barrier 312 NOG 28232471 Pancreatic cancer pancreatic cancer Matrix barrier Many factors that are present in this organoid media, including Noggin, B27 supplement, and TGBβ inhibitor, are known to be potent inhibitors of fibroblast proliferation. Pancreatic_cancer Matrix_barrier 313 TGFB1 28232471 Pancreatic cancer pancreatic cancer Matrix barrier Many factors that are present in this organoid media, including Noggin, B27 supplement, and TGBβ inhibitor, are known to be potent inhibitors of fibroblast proliferation. Pancreatic_cancer Matrix_barrier 314 MRAP 28232471 Pancreatic cancer pancreatic cancer Matrix barrier Many factors that are present in this organoid media, including Noggin, B27 supplement, and TGBβ inhibitor, are known to be potent inhibitors of fibroblast proliferation. Pancreatic_cancer Matrix_barrier 315 IL6 36906534 Pan-cancer squamous cell carcinomas Matrix barrier In PDAC, ECM stiffness induced by CAFs activates ERK pathway and promotes cancer metastasis. In squamous cell carcinoma, IL-6 plays the same role by targeting STAT3/ERK pathway in CAFs Pan-cancer Matrix_barrier 316 STAT3 36906534 Pan-cancer squamous cell carcinomas Matrix barrier In PDAC, ECM stiffness induced by CAFs activates ERK pathway and promotes cancer metastasis. In squamous cell carcinoma, IL-6 plays the same role by targeting STAT3/ERK pathway in CAFs Pan-cancer Matrix_barrier 317 MAPK1 36906534 Pan-cancer squamous cell carcinomas Matrix barrier In PDAC, ECM stiffness induced by CAFs activates ERK pathway and promotes cancer metastasis. In squamous cell carcinoma, IL-6 plays the same role by targeting STAT3/ERK pathway in CAFs Pan-cancer Matrix_barrier 318 C1QB 35029648 Lung cancer lung cancer Matrix barrier Lung apCAFs are shown to directly activate CD4 T cells and produce C1q, which rescues T cells from apoptosis. Deletion of MHCII or C1q in fibroblasts impairs CD4 T cell immunity and accelerates tumor growth. Conversely, inducing C1qbp in CD4 T cells enhances their expansion within tumors, suggesting a novel tumor-suppressive function of lung apCAFs and the importance of in situ MHCII antigen presentation for effective antitumor immunity. Lung_cancer Matrix_barrier 319 C1QC 35029648 Lung cancer lung cancer Matrix barrier Lung apCAFs are shown to directly activate CD4 T cells and produce C1q, which rescues T cells from apoptosis. Deletion of MHCII or C1q in fibroblasts impairs CD4 T cell immunity and accelerates tumor growth. Conversely, inducing C1qbp in CD4 T cells enhances their expansion within tumors, suggesting a novel tumor-suppressive function of lung apCAFs and the importance of in situ MHCII antigen presentation for effective antitumor immunity. Lung_cancer Matrix_barrier 320 C1QA 35029648 Lung cancer lung cancer Matrix barrier Lung apCAFs are shown to directly activate CD4 T cells and produce C1q, which rescues T cells from apoptosis. Deletion of MHCII or C1q in fibroblasts impairs CD4 T cell immunity and accelerates tumor growth. Conversely, inducing C1qbp in CD4 T cells enhances their expansion within tumors, suggesting a novel tumor-suppressive function of lung apCAFs and the importance of in situ MHCII antigen presentation for effective antitumor immunity. Lung_cancer Matrix_barrier 321 CXCL8 38006530 Gastrointestinal cancer Gastric Cancer Matrix barrier Targeting CAF-derived IL-8 may defeat PD-L1 upregulation-mediated immune resistance in GC cells, which provides a novel approach to improve the immunotherapeutic efficacies of patients with GC. Gastrointestinal_cancer Matrix_barrier 322 CD274 38006530 Gastrointestinal cancer Gastric Cancer Matrix barrier Targeting CAF-derived IL-8 may defeat PD-L1 upregulation-mediated immune resistance in GC cells, which provides a novel approach to improve the immunotherapeutic efficacies of patients with GC. Gastrointestinal_cancer Matrix_barrier 323 C1QBP 35029648 Lung cancer lung cancer Matrix barrier Lung apCAFs are shown to directly activate CD4 T cells and produce C1q, which rescues T cells from apoptosis. Deletion of MHCII or C1q in fibroblasts impairs CD4 T cell immunity and accelerates tumor growth. Conversely, inducing C1qbp in CD4 T cells enhances their expansion within tumors, suggesting a novel tumor-suppressive function of lung apCAFs and the importance of in situ MHCII antigen presentation for effective antitumor immunity. Lung_cancer Matrix_barrier 324 CXCL1 20702723 Ovarian cancer ovarian cancer Chemokine CXCL1 functions through CXCR2 to transactivate the EGFR by proteolytic cleavage of HB-EGF, leading to activation of MAPK signalling and increased proliferation of epithelial ovarian cancer (EOC) cells. Ovarian_cancer Chemokine 325 CXCR2 20702723 Ovarian cancer ovarian cancer Chemokine CXCL1 functions through CXCR2 to transactivate the EGFR by proteolytic cleavage of HB-EGF, leading to activation of MAPK signalling and increased proliferation of epithelial ovarian cancer (EOC) cells. Ovarian_cancer Chemokine 326 EGFR 20702723 Ovarian cancer ovarian cancer Chemokine CXCL1 functions through CXCR2 to transactivate the EGFR by proteolytic cleavage of HB-EGF, leading to activation of MAPK signalling and increased proliferation of epithelial ovarian cancer (EOC) cells. Ovarian_cancer Chemokine 327 HBEGF 20702723 Ovarian cancer ovarian cancer Chemokine CXCL1 functions through CXCR2 to transactivate the EGFR by proteolytic cleavage of HB-EGF, leading to activation of MAPK signalling and increased proliferation of epithelial ovarian cancer (EOC) cells. Ovarian_cancer Chemokine 328 MAPK1 20702723 Ovarian cancer ovarian cancer Chemokine CXCL1 functions through CXCR2 to transactivate the EGFR by proteolytic cleavage of HB-EGF, leading to activation of MAPK signalling and increased proliferation of epithelial ovarian cancer (EOC) cells. Ovarian_cancer Chemokine 329 CXCL1 24376747 Ovarian cancer ovarian cancer Chemokine Augmentation of proinflammatory chemokines CXCL1/2, by potentiating NF-κB activation through EGFR-transactivated Akt, contributes to CXCR2-driven ovarian cancer progression. Ovarian_cancer Chemokine 330 CXCL2 24376747 Ovarian cancer ovarian cancer Chemokine Augmentation of proinflammatory chemokines CXCL1/2, by potentiating NF-κB activation through EGFR-transactivated Akt, contributes to CXCR2-driven ovarian cancer progression. Ovarian_cancer Chemokine 331 NFKB1 24376747 Ovarian cancer ovarian cancer Chemokine Augmentation of proinflammatory chemokines CXCL1/2, by potentiating NF-κB activation through EGFR-transactivated Akt, contributes to CXCR2-driven ovarian cancer progression. Ovarian_cancer Chemokine 332 AKT1 24376747 Ovarian cancer ovarian cancer Chemokine Augmentation of proinflammatory chemokines CXCL1/2, by potentiating NF-κB activation through EGFR-transactivated Akt, contributes to CXCR2-driven ovarian cancer progression. Ovarian_cancer Chemokine 333 CXCR2 24376747 Ovarian cancer ovarian cancer Chemokine Augmentation of proinflammatory chemokines CXCL1/2, by potentiating NF-κB activation through EGFR-transactivated Akt, contributes to CXCR2-driven ovarian cancer progression. Ovarian_cancer Chemokine 334 CXCL8 30429105 Ovarian cancer ovarian cancer Chemokine We found that plasminogen activator inhibitor-1 (PAI-1) induced the formation of CAMs, after which CAMs increasingly secreted the oncogenic factors interleukin-8 (IL-8) and C-X-C motif chemokine ligand 5 (CXCL5), further promoting the metastasis of ovarian cancer cells in a feedback loop. After the formation of CAMs, PAI-1 activated the nuclear factor kappa B (NFκB) pathway in the CAMs, thus transcriptionally upregulating the expression of the downstream NFκB targets IL-8 and CXCL5. Ovarian_cancer Chemokine 335 CXCL5 30429105 Ovarian cancer ovarian cancer Chemokine We found that plasminogen activator inhibitor-1 (PAI-1) induced the formation of CAMs, after which CAMs increasingly secreted the oncogenic factors interleukin-8 (IL-8) and C-X-C motif chemokine ligand 5 (CXCL5), further promoting the metastasis of ovarian cancer cells in a feedback loop. After the formation of CAMs, PAI-1 activated the nuclear factor kappa B (NFκB) pathway in the CAMs, thus transcriptionally upregulating the expression of the downstream NFκB targets IL-8 and CXCL5. Ovarian_cancer Chemokine 336 SERPINE1 30429105 Ovarian cancer ovarian cancer Chemokine We found that plasminogen activator inhibitor-1 (PAI-1) induced the formation of CAMs, after which CAMs increasingly secreted the oncogenic factors interleukin-8 (IL-8) and C-X-C motif chemokine ligand 5 (CXCL5), further promoting the metastasis of ovarian cancer cells in a feedback loop. After the formation of CAMs, PAI-1 activated the nuclear factor kappa B (NFκB) pathway in the CAMs, thus transcriptionally upregulating the expression of the downstream NFκB targets IL-8 and CXCL5. Ovarian_cancer Chemokine 337 CXCL8 31793192 Ovarian cancer ovarian cancer Chemokine We found that IL-8 and its receptors CXCR1 and CXCR2 were up-regulated in advanced ovarian serous cancer tissues. Furthermore, the level of IL-8 and its receptors CXCR1 and CXCR2 expression were associated with ovarian cancer stage, grade and lymph node metastasis. Ovarian_cancer Chemokine 338 CXCR1 31793192 Ovarian cancer ovarian cancer Chemokine We found that IL-8 and its receptors CXCR1 and CXCR2 were up-regulated in advanced ovarian serous cancer tissues. Furthermore, the level of IL-8 and its receptors CXCR1 and CXCR2 expression were associated with ovarian cancer stage, grade and lymph node metastasis. Ovarian_cancer Chemokine 339 CXCR2 31793192 Ovarian cancer ovarian cancer Chemokine We found that IL-8 and its receptors CXCR1 and CXCR2 were up-regulated in advanced ovarian serous cancer tissues. Furthermore, the level of IL-8 and its receptors CXCR1 and CXCR2 expression were associated with ovarian cancer stage, grade and lymph node metastasis. Ovarian_cancer Chemokine 340 CXCL11 24014111 Ovarian cancer ovarian cancer Chemokine Taken together, these results demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent therapeutic targets in ovarian cancer. Ovarian_cancer Chemokine 341 CXCR3 24014111 Ovarian cancer ovarian cancer Chemokine Taken together, these results demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent therapeutic targets in ovarian cancer. Ovarian_cancer Chemokine 342 CXCL12 15888687 Ovarian cancer ovarian cancer Chemokine Consequently, strategies aimed at modulating the SDF-1-CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells. Ovarian_cancer Chemokine 343 CXCR4 15888687 Ovarian cancer ovarian cancer Chemokine Consequently, strategies aimed at modulating the SDF-1-CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells. Ovarian_cancer Chemokine 344 ARHGAP10 31445707 Ovarian cancer ovarian cancer Chemokine In summary, these findings suggest that CXCL12/CXCR4 promotes ovarian cancer cell invasion by suppressing ARHGAP10 expression, which is mediated by VEGF/VEGFR2 signaling. Ovarian_cancer Chemokine 345 WNT5A 31932454 Ovarian cancer ovarian cancer Chemokine This study establishes host-derived Wnt5a, expressed by peritoneal mesothelial cells and adipocytes, as a primary regulator of ovarian cancer intraperitoneal metastatic dissemination and identifies Fgr kinase as novel target for inhibition of metastasis. Ovarian_cancer Chemokine 346 FGR 31932454 Ovarian cancer ovarian cancer Chemokine This study establishes host-derived Wnt5a, expressed by peritoneal mesothelial cells and adipocytes, as a primary regulator of ovarian cancer intraperitoneal metastatic dissemination and identifies Fgr kinase as novel target for inhibition of metastasis. Ovarian_cancer Chemokine 347 ACKR3 30051594 Ovarian cancer ovarian cancer Chemokine These findings identify a feed-forward mechanism that sustains activation of the CXCR7/CXCL11 axis under ERα control to induce the epithelial-mesenchymal transition pathway and metastatic behavior of OC cells. Such interplay underlies the complex gene profile heterogeneity of OC that promotes changes in tumor microenvironment and metastatic acquisition. Ovarian_cancer Chemokine 348 CXCL11 30051594 Ovarian cancer ovarian cancer Chemokine These findings identify a feed-forward mechanism that sustains activation of the CXCR7/CXCL11 axis under ERα control to induce the epithelial-mesenchymal transition pathway and metastatic behavior of OC cells. Such interplay underlies the complex gene profile heterogeneity of OC that promotes changes in tumor microenvironment and metastatic acquisition. Ovarian_cancer Chemokine 349 CXCL12 30857971 Ovarian cancer ovarian cancer Chemokine These results indicate that CAF effectively attracts monocytes via the CXCL12/CXCR4 pathway and induces their differentiation to M2 macrophages. Ovarian_cancer Chemokine 350 CXCR4 30857971 Ovarian cancer ovarian cancer Chemokine These results indicate that CAF effectively attracts monocytes via the CXCL12/CXCR4 pathway and induces their differentiation to M2 macrophages. Ovarian_cancer Chemokine 351 CXCL14 32077118 Ovarian cancer ovarian cancer Chemokine In vitro and in vivo experiments both confirmed that overexpression of CXCL14 promoted the ovarian cancer cell proliferation. Moreover, transfection of CXCL14 increased the phosphorylation level of signal transducer and activator of transcription 3 (STAT3), and administration of STAT3 inhibitor III inhibited the tumour-promoting effects of CXCL14. Ovarian_cancer Chemokine 352 STAT3 32077118 Ovarian cancer ovarian cancer Chemokine In vitro and in vivo experiments both confirmed that overexpression of CXCL14 promoted the ovarian cancer cell proliferation. Moreover, transfection of CXCL14 increased the phosphorylation level of signal transducer and activator of transcription 3 (STAT3), and administration of STAT3 inhibitor III inhibited the tumour-promoting effects of CXCL14. Ovarian_cancer Chemokine 353 CXCR6 30049511 Ovarian cancer ovarian cancer Chemokine Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. Ovarian_cancer Chemokine 354 PIK3CB 30049511 Ovarian cancer ovarian cancer Chemokine Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. Ovarian_cancer Chemokine 355 PIK3CA 30049511 Ovarian cancer ovarian cancer Chemokine Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. Ovarian_cancer Chemokine 356 PIK3CG 30049511 Ovarian cancer ovarian cancer Chemokine Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. Ovarian_cancer Chemokine 357 PIK3CD 30049511 Ovarian cancer ovarian cancer Chemokine Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. Ovarian_cancer Chemokine 358 AKT1 30049511 Ovarian cancer ovarian cancer Chemokine Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. Ovarian_cancer Chemokine 359 AKT2 30049511 Ovarian cancer ovarian cancer Chemokine Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. Ovarian_cancer Chemokine 360 AKT3 30049511 Ovarian cancer ovarian cancer Chemokine Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. Ovarian_cancer Chemokine 361 NFKB1 30049511 Ovarian cancer ovarian cancer Chemokine Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. Ovarian_cancer Chemokine 362 NFKB1 33028251 Ovarian cancer ovarian cancer Chemokine In syngeneic ovarian cancer models, increased canonical NF-κB signaling in macrophages promoted anti-tumor TAM phenotypes and increased cytotoxic T cell infiltration, which was sufficient to limit tumor progression. Ovarian_cancer Chemokine 363 CXCL9 27490802 Ovarian cancer ovarian cancer Chemokine In human ovarian cancer cell lines the cyclooxygenase (COX) metabolite Prostaglandin E2 was identified as negative regulator of chemokine secretion, whereas COX inhibition by indomethacin significantly upregulated CXCL9 and CXCL10. In contrast, celecoxib, the only COX inhibitor prospectively evaluated for therapy of ovarian cancer, suppressed NF-κB activation and inhibited chemokine release. Ovarian_cancer Chemokine 364 CXCL10 27490802 Ovarian cancer ovarian cancer Chemokine In human ovarian cancer cell lines the cyclooxygenase (COX) metabolite Prostaglandin E2 was identified as negative regulator of chemokine secretion, whereas COX inhibition by indomethacin significantly upregulated CXCL9 and CXCL10. In contrast, celecoxib, the only COX inhibitor prospectively evaluated for therapy of ovarian cancer, suppressed NF-κB activation and inhibited chemokine release. Ovarian_cancer Chemokine 365 CXCL13 33452206 Ovarian cancer ovarian cancer Chemokine These data define a critical role of CXCL13 in shaping antitumor microenvironment by facilitating the maintenance of CXCR5+CD8+ T cells in TLSs and support a clinical investigation for a combination of CXCL13 and PD-1 blockade therapy in HGSC. Ovarian_cancer Chemokine 366 CXCR5 33452206 Ovarian cancer ovarian cancer Chemokine These data define a critical role of CXCL13 in shaping antitumor microenvironment by facilitating the maintenance of CXCR5+CD8+ T cells in TLSs and support a clinical investigation for a combination of CXCL13 and PD-1 blockade therapy in HGSC. Ovarian_cancer Chemokine 367 CD8A 33452206 Ovarian cancer ovarian cancer Chemokine These data define a critical role of CXCL13 in shaping antitumor microenvironment by facilitating the maintenance of CXCR5+CD8+ T cells in TLSs and support a clinical investigation for a combination of CXCL13 and PD-1 blockade therapy in HGSC. Ovarian_cancer Chemokine 368 PDCD1 33452206 Ovarian cancer ovarian cancer Chemokine These data define a critical role of CXCL13 in shaping antitumor microenvironment by facilitating the maintenance of CXCR5+CD8+ T cells in TLSs and support a clinical investigation for a combination of CXCL13 and PD-1 blockade therapy in HGSC. Ovarian_cancer Chemokine 369 ITGAE 34607898 Ovarian cancer ovarian cancer Chemokine Analysis of The Cancer Genome Atlas (TCGA) (ovarian cancer database revealed CXCR6 to be associated with CD103 and increased patient survival. Functional studies in mouse models of ovarian cancer revealed that CXCR6 is a marker of resident, but not circulatory, tumor-specific memory CD8+ T cells. Ovarian_cancer Chemokine 370 CXCR6 34607898 Ovarian cancer ovarian cancer Chemokine Analysis of The Cancer Genome Atlas (TCGA) (ovarian cancer database revealed CXCR6 to be associated with CD103 and increased patient survival. Functional studies in mouse models of ovarian cancer revealed that CXCR6 is a marker of resident, but not circulatory, tumor-specific memory CD8+ T cells. Ovarian_cancer Chemokine 371 CD8A 34607898 Ovarian cancer ovarian cancer Chemokine Analysis of The Cancer Genome Atlas (TCGA) (ovarian cancer database revealed CXCR6 to be associated with CD103 and increased patient survival. Functional studies in mouse models of ovarian cancer revealed that CXCR6 is a marker of resident, but not circulatory, tumor-specific memory CD8+ T cells. Ovarian_cancer Chemokine 372 CCL2 38475811 Myeloma myeloma Chemokine Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Myeloma Chemokine 373 CCL3 38475811 Myeloma myeloma Chemokine Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Myeloma Chemokine 374 PPBP 38475811 Myeloma myeloma Chemokine Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Myeloma Chemokine 375 CXCL8 38475811 Myeloma myeloma Chemokine Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Myeloma Chemokine 376 CXCL13 38475811 Myeloma myeloma Chemokine Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Myeloma Chemokine 377 CXCL12 38475811 Myeloma myeloma Chemokine Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Myeloma Chemokine 378 CCL5 38475811 Myeloma myeloma Chemokine Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Myeloma Chemokine 379 PF4 38475811 Myeloma myeloma Chemokine Other chemokines, including CXCL4, CCL19, and CXCL10, may aid in recruiting immune cells, increasing their cytotoxicity against cancer cells, and inducing apoptosis of malignant cells. Myeloma Chemokine 380 CCL19 38475811 Myeloma myeloma Chemokine Other chemokines, including CXCL4, CCL19, and CXCL10, may aid in recruiting immune cells, increasing their cytotoxicity against cancer cells, and inducing apoptosis of malignant cells. Myeloma Chemokine 381 CXCL10 38475811 Myeloma myeloma Chemokine Other chemokines, including CXCL4, CCL19, and CXCL10, may aid in recruiting immune cells, increasing their cytotoxicity against cancer cells, and inducing apoptosis of malignant cells. Myeloma Chemokine 382 CXCL1 38458638 Lung cancer lung cancer Chemokine Mechanistically, H-cells expressed low levels of NK-attracting chemokines (CXCL1 and CXCL8), generating poorly infiltrated metastases. Lung_cancer Chemokine 383 CXCL8 38458638 Lung cancer lung cancer Chemokine Mechanistically, H-cells expressed low levels of NK-attracting chemokines (CXCL1 and CXCL8), generating poorly infiltrated metastases. Lung_cancer Chemokine 384 IL2 38360737 Pan-cancer review, pan-cancer Chemokine When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs. Pan-cancer Chemokine 385 CD80 38360737 Pan-cancer review, pan-cancer Chemokine When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs. Pan-cancer Chemokine 386 IL12A 38360737 Pan-cancer review, pan-cancer Chemokine When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs. Pan-cancer Chemokine 387 IL12B 38360737 Pan-cancer review, pan-cancer Chemokine When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs. Pan-cancer Chemokine 388 PTGS2 38059519 Leukemia leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Leukemia Chemokine 389 PTGS2 38059519 lymphoma leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. lymphoma Chemokine 390 CXCR3 38059519 Leukemia leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Leukemia Chemokine 391 CXCR3 38059519 lymphoma leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. lymphoma Chemokine 392 CXCR4 38059519 Leukemia leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Leukemia Chemokine 393 CXCR4 38059519 lymphoma leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. lymphoma Chemokine 394 CXCL10 38059519 Leukemia leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Leukemia Chemokine 395 CXCL10 38059519 lymphoma leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. lymphoma Chemokine 396 CXCL12 38059519 Leukemia leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Leukemia Chemokine 397 CXCL12 38059519 lymphoma leukemia and lymphoma Chemokine Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂-treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. lymphoma Chemokine 398 CXCL8 38006530 Gastrointestinal cancer Gastric Cancer Chemokine Targeting CAF-derived IL-8 may defeat PD-L1 upregulation-mediated immune resistance in GC cells, which provides a novel approach to improve the immunotherapeutic efficacies of patients with GC. Gastrointestinal_cancer Chemokine 399 CD274 38006530 Gastrointestinal cancer Gastric Cancer Chemokine Targeting CAF-derived IL-8 may defeat PD-L1 upregulation-mediated immune resistance in GC cells, which provides a novel approach to improve the immunotherapeutic efficacies of patients with GC. Gastrointestinal_cancer Chemokine 400 CXCL8 38006530 Gastrointestinal cancer Gastric Cancer Chemokine Repertaxin, an IL-8 receptors (CXCR1/2) inhibitor, reduced PD-L1 expression in GC cells by blocking the P38, JNK, and NF-κB pathways. Gastrointestinal_cancer Chemokine 401 NFKB1 38006530 Gastrointestinal cancer Gastric Cancer Chemokine Repertaxin, an IL-8 receptors (CXCR1/2) inhibitor, reduced PD-L1 expression in GC cells by blocking the P38, JNK, and NF-κB pathways. Gastrointestinal_cancer Chemokine 402 CXCR1 38006530 Gastrointestinal cancer Gastric Cancer Chemokine Repertaxin, an IL-8 receptors (CXCR1/2) inhibitor, reduced PD-L1 expression in GC cells by blocking the P38, JNK, and NF-κB pathways. Gastrointestinal_cancer Chemokine 403 CXCR2 38006530 Gastrointestinal cancer Gastric Cancer Chemokine Repertaxin, an IL-8 receptors (CXCR1/2) inhibitor, reduced PD-L1 expression in GC cells by blocking the P38, JNK, and NF-κB pathways. Gastrointestinal_cancer Chemokine 404 CD274 38006530 Gastrointestinal cancer Gastric Cancer Chemokine Repertaxin, an IL-8 receptors (CXCR1/2) inhibitor, reduced PD-L1 expression in GC cells by blocking the P38, JNK, and NF-κB pathways. Gastrointestinal_cancer Chemokine 405 MAPK14 38006530 Gastrointestinal cancer Gastric Cancer Chemokine Repertaxin, an IL-8 receptors (CXCR1/2) inhibitor, reduced PD-L1 expression in GC cells by blocking the P38, JNK, and NF-κB pathways. Gastrointestinal_cancer Chemokine 406 MAPK8 38006530 Gastrointestinal cancer Gastric Cancer Chemokine Repertaxin, an IL-8 receptors (CXCR1/2) inhibitor, reduced PD-L1 expression in GC cells by blocking the P38, JNK, and NF-κB pathways. Gastrointestinal_cancer Chemokine 407 CXCL12 38001512 Bladder cancer bladder cancer Chemokine This study revealed a novel mechanism for the role of CXCL12 in P62-mediated PDL1 autophagic regulation. Combined application of CXCL12 receptor blocker and PD1/PDL1 blocker can more effectively inhibit PDL1 expression and enhance antitumor immune response. Targeting CAFs-derived CXCL12 may provide an effective strategy for immunotherapy in bladder cancer. Bladder_cancer Chemokine 408 SQSTM1 38001512 Bladder cancer bladder cancer Chemokine This study revealed a novel mechanism for the role of CXCL12 in P62-mediated PDL1 autophagic regulation. Combined application of CXCL12 receptor blocker and PD1/PDL1 blocker can more effectively inhibit PDL1 expression and enhance antitumor immune response. Targeting CAFs-derived CXCL12 may provide an effective strategy for immunotherapy in bladder cancer. Bladder_cancer Chemokine 409 PDCD1 38001512 Bladder cancer bladder cancer Chemokine This study revealed a novel mechanism for the role of CXCL12 in P62-mediated PDL1 autophagic regulation. Combined application of CXCL12 receptor blocker and PD1/PDL1 blocker can more effectively inhibit PDL1 expression and enhance antitumor immune response. Targeting CAFs-derived CXCL12 may provide an effective strategy for immunotherapy in bladder cancer. Bladder_cancer Chemokine 410 CD274 38001512 Bladder cancer bladder cancer Chemokine This study revealed a novel mechanism for the role of CXCL12 in P62-mediated PDL1 autophagic regulation. Combined application of CXCL12 receptor blocker and PD1/PDL1 blocker can more effectively inhibit PDL1 expression and enhance antitumor immune response. Targeting CAFs-derived CXCL12 may provide an effective strategy for immunotherapy in bladder cancer. Bladder_cancer Chemokine 411 CXCL12 37872588 Melanoma melanoma Chemokine We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1β. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis. Melanoma Chemokine 412 IL1B 37872588 Melanoma melanoma Chemokine We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1β. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis. Melanoma Chemokine 413 CD274 37872588 Melanoma melanoma Chemokine We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1β. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis. Melanoma Chemokine 414 MYBL2 37865750 Ovarian cancer ovarian cancer Chemokine The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy. Ovarian_cancer Chemokine 415 CCL2 37865750 Ovarian cancer ovarian cancer Chemokine The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy. Ovarian_cancer Chemokine 416 PDCD1 37865750 Ovarian cancer ovarian cancer Chemokine The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy. Ovarian_cancer Chemokine 417 CXCL1 37802708 Colon cancer colorectal cancer Chemokine CXCL1 was upregulated in CRC. Cell experiments demonstrated that CXCL1 overexpression promoted immune escape in CRC. Rescue experiments revealed that the autophagy inducer Rapa could attenuate the inhibitory effect of CXCL1 low expression on immune escape in CRC. Further studies showed that CXCL1 promoted immune escape in CRC by autophagy-mediated MHC-I degradation. Colon_cancer Chemokine 418 CX3CR1 37771579 Colon cancer colon carcinoma Chemokine The CX3CR1 monoclonal antibody reduces migration of tumor cells and decreases secretion of immune suppressive soluble mediators by tumor cells. Colon_cancer Chemokine 419 UBA3 37656220 Lung cancer lung adenocarcinoma Chemokine Blocking UBA3 and the neddylation pathway promoted the accumulation of the phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκBα), inhibiting the gene expression of tumor cell-derived cytokines such as C-C motif chemokine ligand (CCL) 2, C-X-C motif ligand (CXCL)1, CXCL2, colony-stimulating factor (CSF) 1, CSF2 interleukin (IL)-6, and IL-1B. Lung_cancer Chemokine 420 CSF1 37656220 Lung cancer lung adenocarcinoma Chemokine Blocking UBA3 and the neddylation pathway promoted the accumulation of the phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκBα), inhibiting the gene expression of tumor cell-derived cytokines such as C-C motif chemokine ligand (CCL) 2, C-X-C motif ligand (CXCL)1, CXCL2, colony-stimulating factor (CSF) 1, CSF2 interleukin (IL)-6, and IL-1B. Lung_cancer Chemokine 421 CCL2 37656220 Lung cancer lung adenocarcinoma Chemokine Blocking UBA3 and the neddylation pathway promoted the accumulation of the phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκBα), inhibiting the gene expression of tumor cell-derived cytokines such as C-C motif chemokine ligand (CCL) 2, C-X-C motif ligand (CXCL)1, CXCL2, colony-stimulating factor (CSF) 1, CSF2 interleukin (IL)-6, and IL-1B. Lung_cancer Chemokine 422 CXCL1 37656220 Lung cancer lung adenocarcinoma Chemokine Blocking UBA3 and the neddylation pathway promoted the accumulation of the phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκBα), inhibiting the gene expression of tumor cell-derived cytokines such as C-C motif chemokine ligand (CCL) 2, C-X-C motif ligand (CXCL)1, CXCL2, colony-stimulating factor (CSF) 1, CSF2 interleukin (IL)-6, and IL-1B. Lung_cancer Chemokine 423 CXCL2 37656220 Lung cancer lung adenocarcinoma Chemokine Blocking UBA3 and the neddylation pathway promoted the accumulation of the phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκBα), inhibiting the gene expression of tumor cell-derived cytokines such as C-C motif chemokine ligand (CCL) 2, C-X-C motif ligand (CXCL)1, CXCL2, colony-stimulating factor (CSF) 1, CSF2 interleukin (IL)-6, and IL-1B. Lung_cancer Chemokine 424 CSF2 37656220 Lung cancer lung adenocarcinoma Chemokine Blocking UBA3 and the neddylation pathway promoted the accumulation of the phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκBα), inhibiting the gene expression of tumor cell-derived cytokines such as C-C motif chemokine ligand (CCL) 2, C-X-C motif ligand (CXCL)1, CXCL2, colony-stimulating factor (CSF) 1, CSF2 interleukin (IL)-6, and IL-1B. Lung_cancer Chemokine 425 IL6 37656220 Lung cancer lung adenocarcinoma Chemokine Blocking UBA3 and the neddylation pathway promoted the accumulation of the phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκBα), inhibiting the gene expression of tumor cell-derived cytokines such as C-C motif chemokine ligand (CCL) 2, C-X-C motif ligand (CXCL)1, CXCL2, colony-stimulating factor (CSF) 1, CSF2 interleukin (IL)-6, and IL-1B. Lung_cancer Chemokine 426 IL1B 37656220 Lung cancer lung adenocarcinoma Chemokine Blocking UBA3 and the neddylation pathway promoted the accumulation of the phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκBα), inhibiting the gene expression of tumor cell-derived cytokines such as C-C motif chemokine ligand (CCL) 2, C-X-C motif ligand (CXCL)1, CXCL2, colony-stimulating factor (CSF) 1, CSF2 interleukin (IL)-6, and IL-1B. Lung_cancer Chemokine 427 CCL17 37466677 Other cancers skin cancer Chemokine Transcriptomic analysis and functional rescue study confirmed CCL17, CCL20 and CCL22 as the main affected chemokines that mediate the chemotaxis between miR-22 highly expressing keratinocyte tumor cells and Tregs. Other_cancers Chemokine 428 CCL20 37466677 Other cancers skin cancer Chemokine Transcriptomic analysis and functional rescue study confirmed CCL17, CCL20 and CCL22 as the main affected chemokines that mediate the chemotaxis between miR-22 highly expressing keratinocyte tumor cells and Tregs. Other_cancers Chemokine 429 CCL22 37466677 Other cancers skin cancer Chemokine Transcriptomic analysis and functional rescue study confirmed CCL17, CCL20 and CCL22 as the main affected chemokines that mediate the chemotaxis between miR-22 highly expressing keratinocyte tumor cells and Tregs. Other_cancers Chemokine 430 CXCL10 37354983 Colon cancer colorectal cancer Chemokine We found that chemokine ligand 10 (CXCL10) expression correlates with intratumoral CD8+ T cell infiltration and reprograms tumor vasculatures in colorectal cancer. Colon_cancer Chemokine 431 VCAN 37354983 Colon cancer colorectal cancer Chemokine Mechanically, CXCL10 interacts with VCAN to mediate tumor vascular normalization. The VCAN expression correlated inversely with the expression of CXCL10 and the infiltration of CD8+ T cells in CRC. Colon_cancer Chemokine 432 KRT17 37129929 Colon cancer Colorectal Cancer Chemokine Poor infiltration of T lymphocytes has been regarded as a crucial mechanism of tumor immune escape. Here, we demonstrate a protective role of KRT17 in colorectal cancer, where KRT17 reversed the tumor immunosuppressive microenvironment by increasing T-lymphocyte infiltration. Colon_cancer Chemokine 433 CXCL10 37129929 Colon cancer Colorectal Cancer Chemokine Through high-throughput RNA immunoprecipitation sequencing, we found that CXCL10 was the target gene of the N6-methyladenosine (m6A) "reader" YTHDF2. KRT17 synergized with anti-PD-1 for better tumor control in an immunotherapy-resistant murine model. Colon_cancer Chemokine 434 YTHDF2 37129929 Colon cancer Colorectal Cancer Chemokine Through high-throughput RNA immunoprecipitation sequencing, we found that CXCL10 was the target gene of the N6-methyladenosine (m6A) "reader" YTHDF2. KRT17 synergized with anti-PD-1 for better tumor control in an immunotherapy-resistant murine model. Colon_cancer Chemokine 435 IL33 36917642 Liver cancer hepatocellular carcinoma Chemokine IL-33 overexpression inhibited proliferation and repressed the abundance of programmed death ligand 1 (PD-L1) at the transcriptional level by promoting the ubiquitin-dependent degradation of interferon regulatory factor 1 (IRF1). Liver_cancer Chemokine 436 CD274 36917642 Liver cancer hepatocellular carcinoma Chemokine IL-33 overexpression inhibited proliferation and repressed the abundance of programmed death ligand 1 (PD-L1) at the transcriptional level by promoting the ubiquitin-dependent degradation of interferon regulatory factor 1 (IRF1). Liver_cancer Chemokine 437 IRF1 36917642 Liver cancer hepatocellular carcinoma Chemokine IL-33 overexpression inhibited proliferation and repressed the abundance of programmed death ligand 1 (PD-L1) at the transcriptional level by promoting the ubiquitin-dependent degradation of interferon regulatory factor 1 (IRF1). Liver_cancer Chemokine 438 IL6 36646396 Breast cancer breast cancer Chemokine Taken together, our findings suggest a novel mechanism of post-operative metastatic outbreak, where surgery-induced adrenergic and prostanoid signaling increase the secretion of pro-metastatic factors, including IL-6, IL-8, and VEGF, from PT and possibly residual malignant tissue, and thereby prevent residual disease from entering dormancy. Breast_cancer Chemokine 439 CXCL8 36646396 Breast cancer breast cancer Chemokine Taken together, our findings suggest a novel mechanism of post-operative metastatic outbreak, where surgery-induced adrenergic and prostanoid signaling increase the secretion of pro-metastatic factors, including IL-6, IL-8, and VEGF, from PT and possibly residual malignant tissue, and thereby prevent residual disease from entering dormancy. Breast_cancer Chemokine 440 VEGFA 36646396 Breast cancer breast cancer Chemokine Taken together, our findings suggest a novel mechanism of post-operative metastatic outbreak, where surgery-induced adrenergic and prostanoid signaling increase the secretion of pro-metastatic factors, including IL-6, IL-8, and VEGF, from PT and possibly residual malignant tissue, and thereby prevent residual disease from entering dormancy. Breast_cancer Chemokine 441 ANGPTL8 36529524 Renal cancer renal cell carcinoma Chemokine ANGPTL8 is also involved in the production of chemokines that attract immune suppressor cells to the tumor microenvironment. ANGPTL8 sustains the continuous production of chemokines by activating the NF-κB signaling pathway and maintains the undifferentiated state of ccRCC cells. Renal_cancer Chemokine 442 NFKB1 36529524 Renal cancer renal cell carcinoma Chemokine ANGPTL8 is also involved in the production of chemokines that attract immune suppressor cells to the tumor microenvironment. ANGPTL8 sustains the continuous production of chemokines by activating the NF-κB signaling pathway and maintains the undifferentiated state of ccRCC cells. Renal_cancer Chemokine 443 CCL25 36437627 Oral cancer tongue squamous cell carcinoma Chemokine We found that PDGF-BB induces fibroblast activation by facilitating the oversecretion of chemokine CCL25. Further analysis showed that CCL25 derived from activated fibroblasts activated the Akt signaling pathway to promote PD-L1 expression. The activated fibroblasts inhibited T-cell IFN-γ secretion through the CCL25/Akt/PD-L1 pathway, which indirectly inhibited T-cell proliferation. Oral_cancer Chemokine 444 AKT1 36437627 Oral cancer tongue squamous cell carcinoma Chemokine We found that PDGF-BB induces fibroblast activation by facilitating the oversecretion of chemokine CCL25. Further analysis showed that CCL25 derived from activated fibroblasts activated the Akt signaling pathway to promote PD-L1 expression. The activated fibroblasts inhibited T-cell IFN-γ secretion through the CCL25/Akt/PD-L1 pathway, which indirectly inhibited T-cell proliferation. Oral_cancer Chemokine 445 CD274 36437627 Oral cancer tongue squamous cell carcinoma Chemokine We found that PDGF-BB induces fibroblast activation by facilitating the oversecretion of chemokine CCL25. Further analysis showed that CCL25 derived from activated fibroblasts activated the Akt signaling pathway to promote PD-L1 expression. The activated fibroblasts inhibited T-cell IFN-γ secretion through the CCL25/Akt/PD-L1 pathway, which indirectly inhibited T-cell proliferation. Oral_cancer Chemokine 446 IFNG 36437627 Oral cancer tongue squamous cell carcinoma Chemokine We found that PDGF-BB induces fibroblast activation by facilitating the oversecretion of chemokine CCL25. Further analysis showed that CCL25 derived from activated fibroblasts activated the Akt signaling pathway to promote PD-L1 expression. The activated fibroblasts inhibited T-cell IFN-γ secretion through the CCL25/Akt/PD-L1 pathway, which indirectly inhibited T-cell proliferation. Oral_cancer Chemokine 447 DCLK1 36309200 Gastrointestinal cancer gastrointestinal cancer Chemokine We found that DCLK1-/- tumor cells lose their tumorigenicity under immune surveillance. Failed tumor establishment of DCLK1-/- was associated with an increase in infiltration of CD8+ T cells and effector CD4+ T cells, and reduced numbers of MDSCs in the tumor tissue. Furthermore, DCLK1 promoted the up-regulation of C-X-C motif ligand 1, which recruits MDSCs in CRC through chemokine C-X-C motif receptor 2. The ability of in vivo tumor growth of DCLK1-/- tumor cells was rescued by C-X-C motif ligand 1 overexpression. Gastrointestinal_cancer Chemokine 448 CXCL1 36309200 Gastrointestinal cancer gastrointestinal cancer Chemokine We found that DCLK1-/- tumor cells lose their tumorigenicity under immune surveillance. Failed tumor establishment of DCLK1-/- was associated with an increase in infiltration of CD8+ T cells and effector CD4+ T cells, and reduced numbers of MDSCs in the tumor tissue. Furthermore, DCLK1 promoted the up-regulation of C-X-C motif ligand 1, which recruits MDSCs in CRC through chemokine C-X-C motif receptor 2. The ability of in vivo tumor growth of DCLK1-/- tumor cells was rescued by C-X-C motif ligand 1 overexpression. Gastrointestinal_cancer Chemokine 449 CXCR2 36309200 Gastrointestinal cancer gastrointestinal cancer Chemokine We found that DCLK1-/- tumor cells lose their tumorigenicity under immune surveillance. Failed tumor establishment of DCLK1-/- was associated with an increase in infiltration of CD8+ T cells and effector CD4+ T cells, and reduced numbers of MDSCs in the tumor tissue. Furthermore, DCLK1 promoted the up-regulation of C-X-C motif ligand 1, which recruits MDSCs in CRC through chemokine C-X-C motif receptor 2. The ability of in vivo tumor growth of DCLK1-/- tumor cells was rescued by C-X-C motif ligand 1 overexpression. Gastrointestinal_cancer Chemokine 450 HDAC2 36179603 Liver cancer hepatocellular carcinoma Chemokine This study demonstrates that HDAC2 upregulates ACKR3 via STAT1 to induce migration of M2 macrophages and immune escape in HCC. Liver_cancer Chemokine 451 ACKR3 36179603 Liver cancer hepatocellular carcinoma Chemokine This study demonstrates that HDAC2 upregulates ACKR3 via STAT1 to induce migration of M2 macrophages and immune escape in HCC. Liver_cancer Chemokine 452 STAT1 36179603 Liver cancer hepatocellular carcinoma Chemokine This study demonstrates that HDAC2 upregulates ACKR3 via STAT1 to induce migration of M2 macrophages and immune escape in HCC. Liver_cancer Chemokine 453 ZEB1 36076506 Breast cancer triple-negative breast cancer Chemokine ZEB1 induces immunosuppressive cells and chemokines into the tumor microenvironment (TME), leading to the formation of a tumor immunosuppressive microenvironment. Breast_cancer Chemokine 454 GPX2 36002187 Oral cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Oral_cancer Chemokine 455 GPX2 36002187 Lung cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Lung_cancer Chemokine 456 GPX2 36002187 Bladder cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Bladder_cancer Chemokine 457 NFKB1 36002187 Oral cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Oral_cancer Chemokine 458 NFKB1 36002187 Lung cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Lung_cancer Chemokine 459 NFKB1 36002187 Bladder cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Bladder_cancer Chemokine 460 PTGES2 36002187 Oral cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Oral_cancer Chemokine 461 PTGES2 36002187 Lung cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Lung_cancer Chemokine 462 PTGES2 36002187 Bladder cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Bladder_cancer Chemokine 463 IL6 36002187 Oral cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Oral_cancer Chemokine 464 IL6 36002187 Lung cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Lung_cancer Chemokine 465 IL6 36002187 Bladder cancer squamous carcinomas from the oral cavity (OCSCC) and lung (LUSC), and adenocarcinomas of the bladder (BLCA) and lung (LUAD) Chemokine GPX2 inversely correlated with expression of multiple pro- inflammatory cytokines/chemokines and NF-kB activation in cell lines and knockdown of GPX2 led to increased secretion of prostaglandin E2 (PGE2) and interleukin-6. Bladder_cancer Chemokine 466 CCR2 35851856 Lymphoma diffuse large B-cell lymphoma Chemokine Our study demonstrates that CCR2 expression plays an important role in the development of DLBCL by stimulating cell proliferation, migration, and anti-apoptosis. Therefore, the inhibition of CCR2 may be a potential target for anticancer therapy in DLBCL. Lymphoma Chemokine 467 CCL21 35679464 Leukemia chronic lymphocytic leukemia Chemokine By retaining malignant B cells, CCL21 provides a protective environment for their niching and survival, thus allowing tumor evasion and resistance to treatment. Leukemia Chemokine 468 IL15 35615815 Breast cancer breast cancer Chemokine The IL-15Rc-HIF-1α-CX3CL1 signaling pathway serves as a crosstalk between macrophages and tumor cells in the tumor microenvironment of breast cancer. Breast_cancer Chemokine 469 HIF1A 35615815 Breast cancer breast cancer Chemokine The IL-15Rc-HIF-1α-CX3CL1 signaling pathway serves as a crosstalk between macrophages and tumor cells in the tumor microenvironment of breast cancer. Breast_cancer Chemokine 470 CX3CL1 35615815 Breast cancer breast cancer Chemokine The IL-15Rc-HIF-1α-CX3CL1 signaling pathway serves as a crosstalk between macrophages and tumor cells in the tumor microenvironment of breast cancer. Breast_cancer Chemokine 471 HHLA2 35371079 Liver cancer Hepatocellular Carcinoma Chemokine High expression of HHLA2 is an independent prognostic biomarker for HCC patients. It can activate the cell cycle and foster an immunosuppressive tumor microenvironment by enriching exhausted CD8+ T cells. Liver_cancer Chemokine 472 CCL5 35208526 Colon cancer colorectal cancer Chemokine RANTES activity might be associated with angiogenesis, lymphogenesis, and immune escape in CRC. RANTES is an important chemokine that is a part of the chemokine-cytokine network involved in the modulation of TME composition in CRC. Colon_cancer Chemokine 473 CCL17 35025968 Other cancers the Epstein-Barr Virus tumors Chemokine These data suggest that EBV-driven tumors employ dual mechanisms for CCL17 and CCL22 production. Importantly, both in vitro and in vivo Treg migration was effectively blocked by a novel, small molecule antagonist of CCR4, CCR4-351. Antagonism of the CCR4 receptor may thus be an effective means of activating the immune response against a wide spectrum of EBV+ tumors. Other_cancers Chemokine 474 CCL22 35025968 Other cancers the Epstein-Barr Virus tumors Chemokine These data suggest that EBV-driven tumors employ dual mechanisms for CCL17 and CCL22 production. Importantly, both in vitro and in vivo Treg migration was effectively blocked by a novel, small molecule antagonist of CCR4, CCR4-351. Antagonism of the CCR4 receptor may thus be an effective means of activating the immune response against a wide spectrum of EBV+ tumors. Other_cancers Chemokine 475 CCR4 35025968 Other cancers the Epstein-Barr Virus tumors Chemokine These data suggest that EBV-driven tumors employ dual mechanisms for CCL17 and CCL22 production. Importantly, both in vitro and in vivo Treg migration was effectively blocked by a novel, small molecule antagonist of CCR4, CCR4-351. Antagonism of the CCR4 receptor may thus be an effective means of activating the immune response against a wide spectrum of EBV+ tumors. Other_cancers Chemokine 476 ATRX 34951647 Brain cancer glioma Chemokine ATRX loss activates a BRD-dependent immune-suppressive transcriptome and immune escape mechanism in IDH1R132H/p53mut astrocytoma cells Brain_cancer Chemokine 477 IRAK1 34906138 Leukemia acute myeloid leukemia Chemokine IRAK1 orchestrates a previously unknown FGFR1-directed immune escape mechanism in SCLL, through induction of MDSCs via regulation of IFN-γ signaling from leukemia cells, and targeting IRAK1 may provide a means of suppressing tumor growth in this syndrome by restoring immune surveillance. Leukemia Chemokine 478 FGFR1 34906138 Leukemia acute myeloid leukemia Chemokine IRAK1 orchestrates a previously unknown FGFR1-directed immune escape mechanism in SCLL, through induction of MDSCs via regulation of IFN-γ signaling from leukemia cells, and targeting IRAK1 may provide a means of suppressing tumor growth in this syndrome by restoring immune surveillance. Leukemia Chemokine 479 IFNG 34906138 Leukemia acute myeloid leukemia Chemokine IRAK1 orchestrates a previously unknown FGFR1-directed immune escape mechanism in SCLL, through induction of MDSCs via regulation of IFN-γ signaling from leukemia cells, and targeting IRAK1 may provide a means of suppressing tumor growth in this syndrome by restoring immune surveillance. Leukemia Chemokine 480 MIR15A 34678217 Liver cancer Hepatocellular carcinoma Chemokine By reducing CCL22 binding to C-C chemokine receptor type 4 on Tregs, microRNA-15a/16-1 impaired Treg chemotaxis. Liver_cancer Chemokine 481 MIR16-1 34678217 Liver cancer Hepatocellular carcinoma Chemokine By reducing CCL22 binding to C-C chemokine receptor type 4 on Tregs, microRNA-15a/16-1 impaired Treg chemotaxis. Liver_cancer Chemokine 482 CCL22 34678217 Liver cancer Hepatocellular carcinoma Chemokine By reducing CCL22 binding to C-C chemokine receptor type 4 on Tregs, microRNA-15a/16-1 impaired Treg chemotaxis. Liver_cancer Chemokine 483 CXCR4 34678217 Liver cancer Hepatocellular carcinoma Chemokine By reducing CCL22 binding to C-C chemokine receptor type 4 on Tregs, microRNA-15a/16-1 impaired Treg chemotaxis. Liver_cancer Chemokine 484 CXCR4 34659412 Prostate cancer prostate cancer Chemokine Prostate cancer-derived exosomes could reinforce CXCR4 expression in MDSCs through the TLR2/NF-κB signalling pathway, eventually promoting migration of MDSCs into tumor microenvironment in a CXCR4-CXCL12 axis-dependent manner. Prostate_cancer Chemokine 485 TLR2 34659412 Prostate cancer prostate cancer Chemokine Prostate cancer-derived exosomes could reinforce CXCR4 expression in MDSCs through the TLR2/NF-κB signalling pathway, eventually promoting migration of MDSCs into tumor microenvironment in a CXCR4-CXCL12 axis-dependent manner. Prostate_cancer Chemokine 486 NFKB1 34659412 Prostate cancer prostate cancer Chemokine Prostate cancer-derived exosomes could reinforce CXCR4 expression in MDSCs through the TLR2/NF-κB signalling pathway, eventually promoting migration of MDSCs into tumor microenvironment in a CXCR4-CXCL12 axis-dependent manner. Prostate_cancer Chemokine 487 CXCL12 34659412 Prostate cancer prostate cancer Chemokine Prostate cancer-derived exosomes could reinforce CXCR4 expression in MDSCs through the TLR2/NF-κB signalling pathway, eventually promoting migration of MDSCs into tumor microenvironment in a CXCR4-CXCL12 axis-dependent manner. Prostate_cancer Chemokine 488 ELK3 34658341 Gastrointestinal cancer gastric cancer Chemokine Comprehensive analysis identified 176 potential target genes of ELK3, and enrichment analysis showed that ELK3 may regulate Rap1, AMPK, chemokines, VEGF, TNF, and tumor PD-L1/PD-1 signaling (PP < 0.05). The expression of ELK3 was negatively correlated with regulatory T cells, follicular helper T cells, and CD8+T cells in gastric cancer (P < 0.05). Gastrointestinal_cancer Chemokine 489 PRKD3 34545012 Oral cancer oral squamous cell carcinoma Chemokine These results demonstrate that PKD3 promotes the immune escape of OSCC cells by regulating the expression of Fas, PD-L1, MHC-I, transforming growth factor β, CC-chemokine ligand 21, interleukin-10, and plays a key role in reconstructing the tumor immune escape niche. Oral_cancer Chemokine 490 CCL21 34402138 Pancreatic cancer Pancreatic cancer Chemokine Together, our findings suggested that CCL21 in combination with PD-L1 blockade might be an efficient and promising option for the treatment of PC. Pancreatic_cancer Chemokine 491 CXCL8 34286439 Pan-cancer review, pan-cancer Chemokine The autocrine and paracrine modulation of CXCL8 via the chemokine receptors CXCR1/2 promotes several intracellular signaling cascades that fosters tumor-associated inflammation, reprogramming, epithelial-mesenchymal transition, and neovascularization. Pan-cancer Chemokine 492 CXCR1 34286439 Pan-cancer review, pan-cancer Chemokine The autocrine and paracrine modulation of CXCL8 via the chemokine receptors CXCR1/2 promotes several intracellular signaling cascades that fosters tumor-associated inflammation, reprogramming, epithelial-mesenchymal transition, and neovascularization. Pan-cancer Chemokine 493 CXCR2 34286439 Pan-cancer review, pan-cancer Chemokine The autocrine and paracrine modulation of CXCL8 via the chemokine receptors CXCR1/2 promotes several intracellular signaling cascades that fosters tumor-associated inflammation, reprogramming, epithelial-mesenchymal transition, and neovascularization. Pan-cancer Chemokine 494 CCL5 34215748 Liver cancer hepatocellular carcinoma Chemokine Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Liver_cancer Chemokine 495 MAPK14 34215748 Liver cancer hepatocellular carcinoma Chemokine Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Liver_cancer Chemokine 496 MAX 34215748 Liver cancer hepatocellular carcinoma Chemokine Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Liver_cancer Chemokine 497 CXCL1 34195201 Breast cancer Breast Cancer Chemokine Our findings reveal that CXCL1 functions as an autocrine growth factor for BCSCs and elicits primarily tumor progression and immune escape programs. Targeting the CXCL1/CXCR2 axis could restrain the BCSC compartment and improve the treatment of aggressive BC. Breast_cancer Chemokine 498 CXCR2 34195201 Breast cancer Breast Cancer Chemokine Our findings reveal that CXCL1 functions as an autocrine growth factor for BCSCs and elicits primarily tumor progression and immune escape programs. Targeting the CXCL1/CXCR2 axis could restrain the BCSC compartment and improve the treatment of aggressive BC. Breast_cancer Chemokine 499 FLT3LG 33980589 Melanoma melanoma, colorectal cancer Chemokine DNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression. Melanoma Chemokine 500 FLT3LG 33980589 Colon cancer melanoma, colorectal cancer Chemokine DNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression. Colon_cancer Chemokine 501 CLEC9A 33980589 Melanoma melanoma, colorectal cancer Chemokine DNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression. Melanoma Chemokine 502 CLEC9A 33980589 Colon cancer melanoma, colorectal cancer Chemokine DNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression. Colon_cancer Chemokine 503 CXCR2 33751565 Liver cancer hepatocellular carcinoma Chemokine Meanwhile, chronic restraint stress enhanced the expression of C-X-C motif chemokine receptor 2 (CXCR2) and pErk1/2 in bone marrow MDSCs, together with elevated chemokine (C-X-C motif) ligand 5 (CXCL5) expression in tumor tissues. Liver_cancer Chemokine 504 CXCL5 33751565 Liver cancer hepatocellular carcinoma Chemokine Meanwhile, chronic restraint stress enhanced the expression of C-X-C motif chemokine receptor 2 (CXCR2) and pErk1/2 in bone marrow MDSCs, together with elevated chemokine (C-X-C motif) ligand 5 (CXCL5) expression in tumor tissues. Liver_cancer Chemokine 505 POU2F1 33594317 Lung cancer lung cancer Chemokine POU2F1 activates the expression of CRK, further promotes the expression of PD-L1, and finally improves the immune escape in lung cancer. Lung_cancer Chemokine 506 POU5F1 33574085 Brain cancer glioblastoma Chemokine Combined transcription profiling and functional studies of Oct4/Sox2 coexpressing GSCs and differentiated GBM cells demonstrated that Oct4 and Sox2 cooperatively induce an immunosuppressive transcriptome consisting of multiple immunosuppressive checkpoints (i.e., PD-L1, CD70, A2aR, TDO) and dysregulation of cytokines and chemokines that are associated with an immunosuppressive tumor microenvironment. Brain_cancer Chemokine 507 SOX2 33574085 Brain cancer glioblastoma Chemokine Combined transcription profiling and functional studies of Oct4/Sox2 coexpressing GSCs and differentiated GBM cells demonstrated that Oct4 and Sox2 cooperatively induce an immunosuppressive transcriptome consisting of multiple immunosuppressive checkpoints (i.e., PD-L1, CD70, A2aR, TDO) and dysregulation of cytokines and chemokines that are associated with an immunosuppressive tumor microenvironment. Brain_cancer Chemokine 508 CXCL13 33332284 Head and neck cancer head and neck, cervical, and ovarian cancer Chemokine In particular, PD-1hiCD39+ CD4 TILs expressed the exhaustion transcription factor TOX and the chemokine CXCL13 and were tumor antigen specific Head_and_neck_cancer Chemokine 509 CXCL13 33332284 Other cancers head and neck, cervical, and ovarian cancer Chemokine In particular, PD-1hiCD39+ CD4 TILs expressed the exhaustion transcription factor TOX and the chemokine CXCL13 and were tumor antigen specific Other_cancers Chemokine 510 CXCL13 33332284 Ovarian cancer head and neck, cervical, and ovarian cancer Chemokine In particular, PD-1hiCD39+ CD4 TILs expressed the exhaustion transcription factor TOX and the chemokine CXCL13 and were tumor antigen specific Ovarian_cancer Chemokine 511 UBR5 33293516 Ovarian cancer ovarian cancer Chemokine Here, we demonstrate that tumor-derived UBR5, an E3 ligase overexpressed in human OC associated with poor prognosis, is essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines. Ovarian_cancer Chemokine 512 BSG 33177695 Melanoma melanoma and lung cancer Chemokine CD147 deletion in T cells increased the frequency of TRM-like cells and the expression of the T-cell chemokines CXCL9 and CXCL10 in the tumor microenvironment. Melanoma Chemokine 513 BSG 33177695 Lung cancer melanoma and lung cancer Chemokine CD147 deletion in T cells increased the frequency of TRM-like cells and the expression of the T-cell chemokines CXCL9 and CXCL10 in the tumor microenvironment. Lung_cancer Chemokine 514 CXCL9 33177695 Melanoma melanoma and lung cancer Chemokine CD147 deletion in T cells increased the frequency of TRM-like cells and the expression of the T-cell chemokines CXCL9 and CXCL10 in the tumor microenvironment. Melanoma Chemokine 515 CXCL9 33177695 Lung cancer melanoma and lung cancer Chemokine CD147 deletion in T cells increased the frequency of TRM-like cells and the expression of the T-cell chemokines CXCL9 and CXCL10 in the tumor microenvironment. Lung_cancer Chemokine 516 CXCL10 33177695 Melanoma melanoma and lung cancer Chemokine CD147 deletion in T cells increased the frequency of TRM-like cells and the expression of the T-cell chemokines CXCL9 and CXCL10 in the tumor microenvironment. Melanoma Chemokine 517 CXCL10 33177695 Lung cancer melanoma and lung cancer Chemokine CD147 deletion in T cells increased the frequency of TRM-like cells and the expression of the T-cell chemokines CXCL9 and CXCL10 in the tumor microenvironment. Lung_cancer Chemokine 518 EBNA1BP2 33122398 Head and neck cancer Nasopharyngeal carcinoma Chemokine This study attempted to identify the detailed mechanisms of EBNA1 functions as a tumor accelerator to promote NPC immune escape by enhancing chemoattraction of Treg cells. Head_and_neck_cancer Chemokine 519 CCL1 32708690 Pan-cancer review, pan-cancer Chemokine M2b-like macrophages can secrete chemokine (C-C motif) ligand 1 (CCL1) and interleukin-10 (IL-10) to support regulatory cell recruitment and to further shape a tolerogenic microenvironment. Pan-cancer Chemokine 520 IL10 32708690 Pan-cancer review, pan-cancer Chemokine M2b-like macrophages can secrete chemokine (C-C motif) ligand 1 (CCL1) and interleukin-10 (IL-10) to support regulatory cell recruitment and to further shape a tolerogenic microenvironment. Pan-cancer Chemokine 521 ESRRA 32366476 Breast cancer breast cancer Chemokine Overexpression of ERRα in breast cancer bone metastases induced expression of chemokines CCL17 and CCL20 and repressed production of TGFβ3. Breast_cancer Chemokine 522 MAP3K11 32209667 Breast cancer breast cancer Chemokine MLK3 is abundantly expressed in T cells, and its loss alters serum chemokines, cytokines, and CD28 protein expression on T cells and its subsets. MLK3 loss or pharmacological inhibition induces activation of T cells in in vitro, ex vivo, and in vivo conditions, irrespective of T cell activating agents. Breast_cancer Chemokine 523 ROS1 34590036 Lung cancer non–small cell lung cancer Inhibiting target recognition Most ROS1-rearranged NSCLCs have low PD-L1 expression and TMB. The activity of ICI in these tumors is modest. In contrast, chemo-ICI can achieve meaningful activity. Lung_cancer Inhibiting_target_recognition 524 ATG7 38627815 Colon cancer colorectal cancer Inhibiting target recognition ATG7 inhibition restored surface major histocompatibility complex I (MHC-I) levels, causing improved antigen presentation and anti-tumor T cell response by activating reactive oxygen species (ROS)/NF-κB pathway. Colon_cancer Inhibiting_target_recognition 525 HLA-C 38627815 Colon cancer colorectal cancer Inhibiting target recognition ATG7 inhibition restored surface major histocompatibility complex I (MHC-I) levels, causing improved antigen presentation and anti-tumor T cell response by activating reactive oxygen species (ROS)/NF-κB pathway. Colon_cancer Inhibiting_target_recognition 526 HLA-B 38627815 Colon cancer colorectal cancer Inhibiting target recognition ATG7 inhibition restored surface major histocompatibility complex I (MHC-I) levels, causing improved antigen presentation and anti-tumor T cell response by activating reactive oxygen species (ROS)/NF-κB pathway. Colon_cancer Inhibiting_target_recognition 527 HLA-A 38627815 Colon cancer colorectal cancer Inhibiting target recognition ATG7 inhibition restored surface major histocompatibility complex I (MHC-I) levels, causing improved antigen presentation and anti-tumor T cell response by activating reactive oxygen species (ROS)/NF-κB pathway. Colon_cancer Inhibiting_target_recognition 528 FASN 38486485 Liver cancer Hepatocellular Carcinoma Inhibiting target recognition Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Liver_cancer Inhibiting_target_recognition 529 HLA-B 38486485 Liver cancer Hepatocellular Carcinoma Inhibiting target recognition Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Liver_cancer Inhibiting_target_recognition 530 HLA-A 38486485 Liver cancer Hepatocellular Carcinoma Inhibiting target recognition Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Liver_cancer Inhibiting_target_recognition 531 HLA-C 38486485 Liver cancer Hepatocellular Carcinoma Inhibiting target recognition Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Liver_cancer Inhibiting_target_recognition 532 CGAS 38482021 Melanoma melanoma Inhibiting target recognition TH1902 inhibited cell proliferation and triggered apoptosis and senescence in B16-F10 cells in vitro, while inducing several downstream effectors of the cGAS/STING pathway and the expression of MHC-I and PD-L1. This is the first evidence that TH1902 exerts its antitumor activity. Melanoma Inhibiting_target_recognition 533 STING1 38482021 Melanoma melanoma Inhibiting target recognition TH1902 inhibited cell proliferation and triggered apoptosis and senescence in B16-F10 cells in vitro, while inducing several downstream effectors of the cGAS/STING pathway and the expression of MHC-I and PD-L1. This is the first evidence that TH1902 exerts its antitumor activity. Melanoma Inhibiting_target_recognition 534 HLA-A 38482021 Melanoma melanoma Inhibiting target recognition TH1902 inhibited cell proliferation and triggered apoptosis and senescence in B16-F10 cells in vitro, while inducing several downstream effectors of the cGAS/STING pathway and the expression of MHC-I and PD-L1. This is the first evidence that TH1902 exerts its antitumor activity. Melanoma Inhibiting_target_recognition 535 HLA-B 38482021 Melanoma melanoma Inhibiting target recognition TH1902 inhibited cell proliferation and triggered apoptosis and senescence in B16-F10 cells in vitro, while inducing several downstream effectors of the cGAS/STING pathway and the expression of MHC-I and PD-L1. This is the first evidence that TH1902 exerts its antitumor activity. Melanoma Inhibiting_target_recognition 536 HLA-C 38482021 Melanoma melanoma Inhibiting target recognition TH1902 inhibited cell proliferation and triggered apoptosis and senescence in B16-F10 cells in vitro, while inducing several downstream effectors of the cGAS/STING pathway and the expression of MHC-I and PD-L1. This is the first evidence that TH1902 exerts its antitumor activity. Melanoma Inhibiting_target_recognition 537 CD274 38482021 Melanoma melanoma Inhibiting target recognition TH1902 inhibited cell proliferation and triggered apoptosis and senescence in B16-F10 cells in vitro, while inducing several downstream effectors of the cGAS/STING pathway and the expression of MHC-I and PD-L1. This is the first evidence that TH1902 exerts its antitumor activity. Melanoma Inhibiting_target_recognition 538 ESR1 38424542 Melanoma melanoma Inhibiting target recognition Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Melanoma Inhibiting_target_recognition 539 CD244 38424542 Melanoma melanoma Inhibiting target recognition Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Melanoma Inhibiting_target_recognition 540 HLA-A 38424542 Melanoma melanoma Inhibiting target recognition Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Melanoma Inhibiting_target_recognition 541 HLA-B 38424542 Melanoma melanoma Inhibiting target recognition Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Melanoma Inhibiting_target_recognition 542 HLA-C 38424542 Melanoma melanoma Inhibiting target recognition Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Melanoma Inhibiting_target_recognition 543 LILRB1 38393969 Melanoma melanoma Inhibiting target recognition We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that while ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. Melanoma Inhibiting_target_recognition 544 LILRB2 38393969 Melanoma melanoma Inhibiting target recognition We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that while ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. Melanoma Inhibiting_target_recognition 545 HLA-A 38393969 Melanoma melanoma Inhibiting target recognition We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that while ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. Melanoma Inhibiting_target_recognition 546 HLA-B 38393969 Melanoma melanoma Inhibiting target recognition We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that while ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. Melanoma Inhibiting_target_recognition 547 HLA-C 38393969 Melanoma melanoma Inhibiting target recognition We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that while ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. Melanoma Inhibiting_target_recognition 548 EZH2 38265267 Lung cancer lung squamous cell carcinomas Inhibiting target recognition Our in vitro experiments using two-dimensional human cancer cell lines as well as three-dimensional murine and patient-derived organoids treated with two inhibitors of the EZH2 plus IFNγ showed that EZH2 inhibition leads to expression of both MHC class I and II (MHCI/II) expression at both the mRNA and protein levels. Lung_cancer Inhibiting_target_recognition 549 IFNB1 38265267 Lung cancer lung squamous cell carcinomas Inhibiting target recognition Our in vitro experiments using two-dimensional human cancer cell lines as well as three-dimensional murine and patient-derived organoids treated with two inhibitors of the EZH2 plus IFNγ showed that EZH2 inhibition leads to expression of both MHC class I and II (MHCI/II) expression at both the mRNA and protein levels. Lung_cancer Inhibiting_target_recognition 550 HLA-DMA 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 551 HLA-DMB 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 552 HLA-DOA 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 553 HLA-DOB 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 554 HLA-DPA1 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 555 HLA-DPB1 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 556 HLA-DQA1 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 557 HLA-DQA2 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 558 HLA-DQB1 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 559 HLA-DQB2 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 560 HLA-DRA 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 561 HLA-DRB1 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 562 HLA-DRB3 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 563 HLA-DRB4 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 564 HLA-DRB5 33767702 Pan-cancer review, pan-cancer Inhibiting target recognition MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Pan-cancer Inhibiting_target_recognition 565 RGS1 38264343 Lung cancer renal and lung murine subcutaneous tumors Inhibiting target recognition Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Lung_cancer Inhibiting_target_recognition 566 RGS1 38264343 Renal cancer renal and lung murine subcutaneous tumors Inhibiting target recognition Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Renal_cancer Inhibiting_target_recognition 567 ATF3 38264343 Lung cancer renal and lung murine subcutaneous tumors Inhibiting target recognition Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Lung_cancer Inhibiting_target_recognition 568 ATF3 38264343 Renal cancer renal and lung murine subcutaneous tumors Inhibiting target recognition Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Renal_cancer Inhibiting_target_recognition 569 IFNGR1 38264343 Lung cancer renal and lung murine subcutaneous tumors Inhibiting target recognition Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Lung_cancer Inhibiting_target_recognition 570 IFNGR1 38264343 Renal cancer renal and lung murine subcutaneous tumors Inhibiting target recognition Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Renal_cancer Inhibiting_target_recognition 571 ESR1 38229155 Bone cancer osteosarcoma Inhibiting target recognition Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Bone_cancer Inhibiting_target_recognition 572 STC2 38229155 Bone cancer osteosarcoma Inhibiting target recognition Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Bone_cancer Inhibiting_target_recognition 573 HLA-A 38229155 Bone cancer osteosarcoma Inhibiting target recognition Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Bone_cancer Inhibiting_target_recognition 574 HLA-B 38229155 Bone cancer osteosarcoma Inhibiting target recognition Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Bone_cancer Inhibiting_target_recognition 575 HLA-C 38229155 Bone cancer osteosarcoma Inhibiting target recognition Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Bone_cancer Inhibiting_target_recognition 576 NDRG1 38228036 Pancreatic cancer pancreatic ductal adenocarcinoma Inhibiting target recognition Here, we identified a previously undescribed role of NDRG1 in activating major histocompatibility complex class 1 (MHC-1) expression in pancreatic ductal adenocarcinoma (PDAC) cells through lysosomal-autophagy-dependent degradation. Pancreatic_cancer Inhibiting_target_recognition 577 HLA-A 38177410 Head and neck cancer head and neck squamous cell carcinomas Inhibiting target recognition Mechanistically, HNSCC cells are usually defective in the expression of MHC-I associated APM, while this transcriptional pathway is critical for the activation of tumor-killing effector T-cells. Head_and_neck_cancer Inhibiting_target_recognition 578 HLA-B 38177410 Head and neck cancer head and neck squamous cell carcinomas Inhibiting target recognition Mechanistically, HNSCC cells are usually defective in the expression of MHC-I associated APM, while this transcriptional pathway is critical for the activation of tumor-killing effector T-cells. Head_and_neck_cancer Inhibiting_target_recognition 579 HLA-C 38177410 Head and neck cancer head and neck squamous cell carcinomas Inhibiting target recognition Mechanistically, HNSCC cells are usually defective in the expression of MHC-I associated APM, while this transcriptional pathway is critical for the activation of tumor-killing effector T-cells. Head_and_neck_cancer Inhibiting_target_recognition 580 PPT1 38133710 Liver cancer hepatocellular carcinoma Inhibiting target recognition Inhibition of PPT1 potentiates the effects of anti-PD-1 immunotherapy by increasing the expression of major histocompatibility complex (MHC)-I at the surface of liver cancer cells and modulates immunity through recolonization and activation of cytotoxic CD8+ lymphocytes. Liver_cancer Inhibiting_target_recognition 581 PDCD1 38133710 Liver cancer hepatocellular carcinoma Inhibiting target recognition Inhibition of PPT1 potentiates the effects of anti-PD-1 immunotherapy by increasing the expression of major histocompatibility complex (MHC)-I at the surface of liver cancer cells and modulates immunity through recolonization and activation of cytotoxic CD8+ lymphocytes. Liver_cancer Inhibiting_target_recognition 582 PIKFYVE 38011559 Pancreatic cancer pancreatic cancer Inhibiting target recognition Here, we found that genetic or pharmacologic inhibition of the lipid kinase PIKfyve, a regulator of autophagic flux and lysosomal biogenesis, upregulated surface expression of major histocompatibility complex class I (MHC-I) in cancer cells via impairing autophagic flux, resulting in enhanced cancer cell killing mediated by CD8+ T cells. Pancreatic_cancer Inhibiting_target_recognition 583 HLA-A 38011559 Pancreatic cancer pancreatic cancer Inhibiting target recognition Here, we found that genetic or pharmacologic inhibition of the lipid kinase PIKfyve, a regulator of autophagic flux and lysosomal biogenesis, upregulated surface expression of major histocompatibility complex class I (MHC-I) in cancer cells via impairing autophagic flux, resulting in enhanced cancer cell killing mediated by CD8+ T cells. Pancreatic_cancer Inhibiting_target_recognition 584 HLA-B 38011559 Pancreatic cancer pancreatic cancer Inhibiting target recognition Here, we found that genetic or pharmacologic inhibition of the lipid kinase PIKfyve, a regulator of autophagic flux and lysosomal biogenesis, upregulated surface expression of major histocompatibility complex class I (MHC-I) in cancer cells via impairing autophagic flux, resulting in enhanced cancer cell killing mediated by CD8+ T cells. Pancreatic_cancer Inhibiting_target_recognition 585 HLA-C 38011559 Pancreatic cancer pancreatic cancer Inhibiting target recognition Here, we found that genetic or pharmacologic inhibition of the lipid kinase PIKfyve, a regulator of autophagic flux and lysosomal biogenesis, upregulated surface expression of major histocompatibility complex class I (MHC-I) in cancer cells via impairing autophagic flux, resulting in enhanced cancer cell killing mediated by CD8+ T cells. Pancreatic_cancer Inhibiting_target_recognition 586 NFE2L2 37839356 Lung cancer lung cancer Inhibiting target recognition In this context, we found that in human cancer, NRF2-activated cells are highly immunoedited, which allows the cancer cells to escape immune surveillance and develop into malignant tumours. This immunoediting takes the form of reduced antigen presentation by the MHC-I complex, coupled with reduced expression of activating ligands for NK cells. Lung_cancer Inhibiting_target_recognition 587 CD274 37791898 Breast cancer triple-negative breast cancer Inhibiting target recognition This study demonstrates that heterogeneous MHC-I expression drives resistance to anti-PD-L1 therapy and exposes NKG2A on NK cells as a target to overcome resistance. Breast_cancer Inhibiting_target_recognition 588 KLRC1 37791898 Breast cancer triple-negative breast cancer Inhibiting target recognition This study demonstrates that heterogeneous MHC-I expression drives resistance to anti-PD-L1 therapy and exposes NKG2A on NK cells as a target to overcome resistance. Breast_cancer Inhibiting_target_recognition 589 CGAS 37760436 Colon cancer colon adenocarcinoma Inhibiting target recognition Inhibition of the cGAS-STING pathway, pharmacologically or with siRNA, blunted the increase in MHC-I and PD-L1 surface and gene expression following MR. Colon_cancer Inhibiting_target_recognition 590 STING1 37760436 Colon cancer colon adenocarcinoma Inhibiting target recognition Inhibition of the cGAS-STING pathway, pharmacologically or with siRNA, blunted the increase in MHC-I and PD-L1 surface and gene expression following MR. Colon_cancer Inhibiting_target_recognition 591 DUX4 37747887 Other cancers testicular teratocarcinoma Inhibiting target recognition DUX4 is a key regulator of zygotic genome activation in human embryos, whereas misexpression of DUX4 causes facioscapulohumeral muscular dystrophy (FSHD) and is associated with MHC-I suppression and immune evasion in cancer. Other_cancers Inhibiting_target_recognition 592 CAMP 37582744 Melanoma melanoma Inhibiting target recognition Mechanistic studies indicated that 5-NL's induced MHC-I expression was inhibited by pharmacologically preventing cAMP Response Element-Binding Protein (CREB) phosphorylation. Melanoma Inhibiting_target_recognition 593 COL2A1 37365574 Colon cancer colon cancer Inhibiting target recognition Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11-/- mice or Il11-/- mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. Colon_cancer Inhibiting_target_recognition 594 NR0B1 37365574 Colon cancer colon cancer Inhibiting target recognition Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11-/- mice or Il11-/- mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. Colon_cancer Inhibiting_target_recognition 595 IL11 37365574 Colon cancer colon cancer Inhibiting target recognition Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11-/- mice or Il11-/- mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. Colon_cancer Inhibiting_target_recognition 596 STAT3 37365574 Colon cancer colon cancer Inhibiting target recognition Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11-/- mice or Il11-/- mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. Colon_cancer Inhibiting_target_recognition 597 IFNG 37365574 Colon cancer colon cancer Inhibiting target recognition Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11-/- mice or Il11-/- mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. Colon_cancer Inhibiting_target_recognition 598 STAT1 37365574 Colon cancer colon cancer Inhibiting target recognition Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11-/- mice or Il11-/- mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. Colon_cancer Inhibiting_target_recognition 599 EZH2 37333199 Lung cancer lung squamous cell carcinomas Inhibiting target recognition Our in vitro experiments using 2D human cancer cell lines as well as 3D murine and patient derived organoids treated with two inhibitors of the EZH2 plus interferon-γ (IFNγ) showed that EZH2 inhibition leads to expression of both major histocompatibility complex class I and II (MHCI/II) expression at both the mRNA and protein levels. Lung_cancer Inhibiting_target_recognition 600 IFNG 37333199 Lung cancer lung squamous cell carcinomas Inhibiting target recognition Our in vitro experiments using 2D human cancer cell lines as well as 3D murine and patient derived organoids treated with two inhibitors of the EZH2 plus interferon-γ (IFNγ) showed that EZH2 inhibition leads to expression of both major histocompatibility complex class I and II (MHCI/II) expression at both the mRNA and protein levels. Lung_cancer Inhibiting_target_recognition 601 TLR3 37283287 Bladder cancer bladder cancer Inhibiting target recognition Besides, after FGFR3 knockout with siRNA in RT112 and UMUC14 cells, the TLR3/NF-kB pathway was significantly activated and was accompanied by upregulation of MHC-I and PD-L1 gene expression. Bladder_cancer Inhibiting_target_recognition 602 NFKB1 37283287 Bladder cancer bladder cancer Inhibiting target recognition Besides, after FGFR3 knockout with siRNA in RT112 and UMUC14 cells, the TLR3/NF-kB pathway was significantly activated and was accompanied by upregulation of MHC-I and PD-L1 gene expression. Bladder_cancer Inhibiting_target_recognition 603 CD274 37283287 Bladder cancer bladder cancer Inhibiting target recognition Besides, after FGFR3 knockout with siRNA in RT112 and UMUC14 cells, the TLR3/NF-kB pathway was significantly activated and was accompanied by upregulation of MHC-I and PD-L1 gene expression. Bladder_cancer Inhibiting_target_recognition 604 PPP2CA 37219874 Brain cancer Glioblastoma Inhibiting target recognition Genetic ablation of PP2Ac in glioma cells enhanced double-stranded DNA (dsDNA) production and cGAS-type I IFN signaling, MHC-I expression, and tumor mutational burden. Brain_cancer Inhibiting_target_recognition 605 LINC01232 37097629 Brain cancer Glioblastoma Inhibiting target recognition This study reveals the existence of critical molecular crosstalk between TAMs and glioma mediates through the LINC01232/E2F2/NBR1/MHC-I axis to support malignant tumor growth, indicating that targeting this axis may have therapeutic potential. Brain_cancer Inhibiting_target_recognition 606 E2F2 37097630 Brain cancer Glioblastoma Inhibiting target recognition This study reveals the existence of critical molecular crosstalk between TAMs and glioma mediates through the LINC01232/E2F2/NBR1/MHC-I axis to support malignant tumor growth, indicating that targeting this axis may have therapeutic potential. Brain_cancer Inhibiting_target_recognition 607 NBR1 37097630 Brain cancer Glioblastoma Inhibiting target recognition This study reveals the existence of critical molecular crosstalk between TAMs and glioma mediates through the LINC01232/E2F2/NBR1/MHC-I axis to support malignant tumor growth, indicating that targeting this axis may have therapeutic potential. Brain_cancer Inhibiting_target_recognition 608 HLA-A 37097630 Brain cancer Glioblastoma Inhibiting target recognition This study reveals the existence of critical molecular crosstalk between TAMs and glioma mediates through the LINC01232/E2F2/NBR1/MHC-I axis to support malignant tumor growth, indicating that targeting this axis may have therapeutic potential. Brain_cancer Inhibiting_target_recognition 609 HLA-B 37097630 Brain cancer Glioblastoma Inhibiting target recognition This study reveals the existence of critical molecular crosstalk between TAMs and glioma mediates through the LINC01232/E2F2/NBR1/MHC-I axis to support malignant tumor growth, indicating that targeting this axis may have therapeutic potential. Brain_cancer Inhibiting_target_recognition 610 HLA-C 37097630 Brain cancer Glioblastoma Inhibiting target recognition This study reveals the existence of critical molecular crosstalk between TAMs and glioma mediates through the LINC01232/E2F2/NBR1/MHC-I axis to support malignant tumor growth, indicating that targeting this axis may have therapeutic potential. Brain_cancer Inhibiting_target_recognition 611 CGAS 37066240 Colon cancer colorectal cancer Inhibiting target recognition Inhibition of the cGAS-STING pathway, pharmacologically or with siRNA, blunted the increase in MHC-I and PD-L1 surface and gene expression following methionine restriction. This indicated that the cGAS-STING pathway in particular, and interferon in general, is playing a role in the immune response to methionine restriction. Colon_cancer Inhibiting_target_recognition 612 STING1 37066240 Colon cancer colorectal cancer Inhibiting target recognition Inhibition of the cGAS-STING pathway, pharmacologically or with siRNA, blunted the increase in MHC-I and PD-L1 surface and gene expression following methionine restriction. This indicated that the cGAS-STING pathway in particular, and interferon in general, is playing a role in the immune response to methionine restriction. Colon_cancer Inhibiting_target_recognition 613 EHMT2 36971192 Brain cancer glioblastoma Inhibiting target recognition G9a inhibition decreased PD-L1 and increased MHC-I expressions by inactivating Notch pathway companying stemness decrease in GSCs. Mechanistically, G9a bound to Fbxw7, a Notch suppressor, to inhibit gene transcription through H3K9me2 of Fbxw7 promotor. Brain_cancer Inhibiting_target_recognition 614 NOTCH1 36971192 Brain cancer glioblastoma Inhibiting target recognition G9a inhibition decreased PD-L1 and increased MHC-I expressions by inactivating Notch pathway companying stemness decrease in GSCs. Mechanistically, G9a bound to Fbxw7, a Notch suppressor, to inhibit gene transcription through H3K9me2 of Fbxw7 promotor. Brain_cancer Inhibiting_target_recognition 615 NOTCH2 36971192 Brain cancer glioblastoma Inhibiting target recognition G9a inhibition decreased PD-L1 and increased MHC-I expressions by inactivating Notch pathway companying stemness decrease in GSCs. Mechanistically, G9a bound to Fbxw7, a Notch suppressor, to inhibit gene transcription through H3K9me2 of Fbxw7 promotor. Brain_cancer Inhibiting_target_recognition 616 NOTCH3 36971192 Brain cancer glioblastoma Inhibiting target recognition G9a inhibition decreased PD-L1 and increased MHC-I expressions by inactivating Notch pathway companying stemness decrease in GSCs. Mechanistically, G9a bound to Fbxw7, a Notch suppressor, to inhibit gene transcription through H3K9me2 of Fbxw7 promotor. Brain_cancer Inhibiting_target_recognition 617 NOTCH4 36971192 Brain cancer glioblastoma Inhibiting target recognition G9a inhibition decreased PD-L1 and increased MHC-I expressions by inactivating Notch pathway companying stemness decrease in GSCs. Mechanistically, G9a bound to Fbxw7, a Notch suppressor, to inhibit gene transcription through H3K9me2 of Fbxw7 promotor. Brain_cancer Inhibiting_target_recognition 618 FBXW7 36971192 Brain cancer glioblastoma Inhibiting target recognition G9a inhibition decreased PD-L1 and increased MHC-I expressions by inactivating Notch pathway companying stemness decrease in GSCs. Mechanistically, G9a bound to Fbxw7, a Notch suppressor, to inhibit gene transcription through H3K9me2 of Fbxw7 promotor. Brain_cancer Inhibiting_target_recognition 619 IFNA1 36610139 Liver cancer hepatocellular carcinoma Inhibiting target recognition An in vitro analysis demonstrated the susceptibility of TP-pretreated hepatocytes to NK-cell-mediated cytotoxicity, an effect that was significantly attenuated by the induction of hepatocyte MHC-I molecules by IFN-α. Liver_cancer Inhibiting_target_recognition 620 TGFB2 36776837 Brain cancer glioblastoma Inhibiting target recognition A TGF-β2 inhibitory oligodeoxynucleotide, TIO3 could efficiently downregulate the expression of TGF-β2 while increase the MHC-I's expression in GL261 and U251 glioma cells in vitro. Brain_cancer Inhibiting_target_recognition 621 CEMIP 36596591 Colon cancer colorectal cancer Inhibiting target recognition We reported that CEMIP specifically downregulated the expression of MHC-I on the surface of murine and human colon cancer cells, hindering the cytotoxicity of CD8+ T cells. We also demonstrated that CEMIP restricted CD8+ T-cell antitumor activities both in vitro and in vivo due to impaired MHC-I-mediated antigen presentation. Colon_cancer Inhibiting_target_recognition 622 HLA-A 36596591 Colon cancer colorectal cancer Inhibiting target recognition We reported that CEMIP specifically downregulated the expression of MHC-I on the surface of murine and human colon cancer cells, hindering the cytotoxicity of CD8+ T cells. We also demonstrated that CEMIP restricted CD8+ T-cell antitumor activities both in vitro and in vivo due to impaired MHC-I-mediated antigen presentation. Colon_cancer Inhibiting_target_recognition 623 HLA-B 36596591 Colon cancer colorectal cancer Inhibiting target recognition We reported that CEMIP specifically downregulated the expression of MHC-I on the surface of murine and human colon cancer cells, hindering the cytotoxicity of CD8+ T cells. We also demonstrated that CEMIP restricted CD8+ T-cell antitumor activities both in vitro and in vivo due to impaired MHC-I-mediated antigen presentation. Colon_cancer Inhibiting_target_recognition 624 HLA-C 36596591 Colon cancer colorectal cancer Inhibiting target recognition We reported that CEMIP specifically downregulated the expression of MHC-I on the surface of murine and human colon cancer cells, hindering the cytotoxicity of CD8+ T cells. We also demonstrated that CEMIP restricted CD8+ T-cell antitumor activities both in vitro and in vivo due to impaired MHC-I-mediated antigen presentation. Colon_cancer Inhibiting_target_recognition 625 TAP1 36458012 Melanoma melanoma Inhibiting target recognition Here, we show that ACB1801 upregulates the mRNA expression of several proteins of the MHC-I such as Transporter Associated with antigen Processing TAP1 and 2, Tapasin and Lmp2 (hereafter referred to as MHC-I signature) in melanoma cells. Melanoma Inhibiting_target_recognition 626 TAP2 36458012 Melanoma melanoma Inhibiting target recognition Here, we show that ACB1801 upregulates the mRNA expression of several proteins of the MHC-I such as Transporter Associated with antigen Processing TAP1 and 2, Tapasin and Lmp2 (hereafter referred to as MHC-I signature) in melanoma cells. Melanoma Inhibiting_target_recognition 627 PSMB9 36458012 Melanoma melanoma Inhibiting target recognition Here, we show that ACB1801 upregulates the mRNA expression of several proteins of the MHC-I such as Transporter Associated with antigen Processing TAP1 and 2, Tapasin and Lmp2 (hereafter referred to as MHC-I signature) in melanoma cells. Melanoma Inhibiting_target_recognition 628 TAPBP 36458012 Melanoma melanoma Inhibiting target recognition Here, we show that ACB1801 upregulates the mRNA expression of several proteins of the MHC-I such as Transporter Associated with antigen Processing TAP1 and 2, Tapasin and Lmp2 (hereafter referred to as MHC-I signature) in melanoma cells. Melanoma Inhibiting_target_recognition 629 CH25H 36378658 Pancreatic cancer Pancreatic Cancer Inhibiting target recognition Mechanistically, the loss of CH25H promoted autophagy resulting in downregulation of MHC-I and decreased CD8+ T-cell tumor infiltration. Pancreatic_cancer Inhibiting_target_recognition 630 HLA-A 36378658 Pancreatic cancer Pancreatic Cancer Inhibiting target recognition Mechanistically, the loss of CH25H promoted autophagy resulting in downregulation of MHC-I and decreased CD8+ T-cell tumor infiltration. Pancreatic_cancer Inhibiting_target_recognition 631 HLA-B 36378658 Pancreatic cancer Pancreatic Cancer Inhibiting target recognition Mechanistically, the loss of CH25H promoted autophagy resulting in downregulation of MHC-I and decreased CD8+ T-cell tumor infiltration. Pancreatic_cancer Inhibiting_target_recognition 632 HLA-C 36378658 Pancreatic cancer Pancreatic Cancer Inhibiting target recognition Mechanistically, the loss of CH25H promoted autophagy resulting in downregulation of MHC-I and decreased CD8+ T-cell tumor infiltration. Pancreatic_cancer Inhibiting_target_recognition 633 IL6 35921790 Colon cancer colorectal cancer Inhibiting target recognition High level of IL-6 was found in colitis model, with down-regulation of MHC-I molecules. In in vitro experiments, we found that IL-6 may act as a negative regulator in IFNγ-STAT1-MHC-I signaling. In addition, vivo trials also confirmed that MHC-I mRNA level was negatively related to the existence of IL-6. Colon_cancer Inhibiting_target_recognition 634 NOTCH1 35803280 Brain cancer glioblastoma Inhibiting target recognition Loss of Notch activity in a mouse model of glioma impairs MHC-I and cytokine expression and curtails the recruitment of anti-tumor immune cell populations in favor of immunosuppressive tumor-associated microglia/macrophages (TAMs). Brain_cancer Inhibiting_target_recognition 635 NOTCH2 35803280 Brain cancer glioblastoma Inhibiting target recognition Loss of Notch activity in a mouse model of glioma impairs MHC-I and cytokine expression and curtails the recruitment of anti-tumor immune cell populations in favor of immunosuppressive tumor-associated microglia/macrophages (TAMs). Brain_cancer Inhibiting_target_recognition 636 NOTCH3 35803280 Brain cancer glioblastoma Inhibiting target recognition Loss of Notch activity in a mouse model of glioma impairs MHC-I and cytokine expression and curtails the recruitment of anti-tumor immune cell populations in favor of immunosuppressive tumor-associated microglia/macrophages (TAMs). Brain_cancer Inhibiting_target_recognition 637 NOTCH4 35803280 Brain cancer glioblastoma Inhibiting target recognition Loss of Notch activity in a mouse model of glioma impairs MHC-I and cytokine expression and curtails the recruitment of anti-tumor immune cell populations in favor of immunosuppressive tumor-associated microglia/macrophages (TAMs). Brain_cancer Inhibiting_target_recognition 638 XBP1 35794100 Oral cancer tongue squamous cell carcinoma, non-small cell lung cancer, osteosarcoma, melanoma Inhibiting target recognition XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Oral_cancer Inhibiting_target_recognition 639 XBP1 35794100 Lung cancer tongue squamous cell carcinoma, non-small cell lung cancer, osteosarcoma, melanoma Inhibiting target recognition XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Lung_cancer Inhibiting_target_recognition 640 XBP1 35794100 Bone cancer tongue squamous cell carcinoma, non-small cell lung cancer, osteosarcoma, melanoma Inhibiting target recognition XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Bone_cancer Inhibiting_target_recognition 641 XBP1 35794100 Melanoma tongue squamous cell carcinoma, non-small cell lung cancer, osteosarcoma, melanoma Inhibiting target recognition XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Melanoma Inhibiting_target_recognition 642 TPP2 35794100 Oral cancer tongue squamous cell carcinoma, non-small cell lung cancer, osteosarcoma, melanoma Inhibiting target recognition XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Oral_cancer Inhibiting_target_recognition 643 TPP2 35794100 Lung cancer tongue squamous cell carcinoma, non-small cell lung cancer, osteosarcoma, melanoma Inhibiting target recognition XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Lung_cancer Inhibiting_target_recognition 644 TPP2 35794100 Bone cancer tongue squamous cell carcinoma, non-small cell lung cancer, osteosarcoma, melanoma Inhibiting target recognition XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Bone_cancer Inhibiting_target_recognition 645 TPP2 35794100 Melanoma tongue squamous cell carcinoma, non-small cell lung cancer, osteosarcoma, melanoma Inhibiting target recognition XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Melanoma Inhibiting_target_recognition 646 KDM1A 35691495 Head and neck cancer head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Head_and_neck_cancer Inhibiting_target_recognition 647 KDM1A 35691495 Lung cancer head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Lung_cancer Inhibiting_target_recognition 648 KDM1A 35691495 Melanoma head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Melanoma Inhibiting_target_recognition 649 KDM1A 35691495 Bone cancer head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Bone_cancer Inhibiting_target_recognition 650 KDM1A 35691495 Oral cancer head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Oral_cancer Inhibiting_target_recognition 651 SCLC1 35691495 Head and neck cancer head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Head_and_neck_cancer Inhibiting_target_recognition 652 SCLC1 35691495 Lung cancer head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Lung_cancer Inhibiting_target_recognition 653 SCLC1 35691495 Melanoma head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Melanoma Inhibiting_target_recognition 654 SCLC1 35691495 Bone cancer head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Bone_cancer Inhibiting_target_recognition 655 SCLC1 35691495 Oral cancer head and neck squamous cell carcinomas, non-small cell lung cancer, melanoma, tongue squamous cell carcinoma, osteosarcoma Inhibiting target recognition We found that targeted inhibition of LSD1 in SCLC restores MHC-I cell surface expression and transcriptionally activates genes encoding the antigen presentation pathway. Oral_cancer Inhibiting_target_recognition 656 HLA-A 35562811 Breast cancer breast cancer Inhibiting target recognition The two oncogenic human gammaherpesviruses, Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), both downregulate immune surface molecules, such as MHC-I, ICAM-1, and B7-2, enabling them to evade T-cell and natural killer cell immunity. Breast_cancer Inhibiting_target_recognition 657 HLA-B 35562811 Breast cancer breast cancer Inhibiting target recognition The two oncogenic human gammaherpesviruses, Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), both downregulate immune surface molecules, such as MHC-I, ICAM-1, and B7-2, enabling them to evade T-cell and natural killer cell immunity. Breast_cancer Inhibiting_target_recognition 658 HLA-C 35562811 Breast cancer breast cancer Inhibiting target recognition The two oncogenic human gammaherpesviruses, Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), both downregulate immune surface molecules, such as MHC-I, ICAM-1, and B7-2, enabling them to evade T-cell and natural killer cell immunity. Breast_cancer Inhibiting_target_recognition 659 CD4 38609101 Lung cancer lung cancer Inhibiting target recognition Very interestingly, our findings also revealed that QAPHA upregulated major histocompatibility complex class II (MHC-II) expression on TC-1 tumor cells both in vitro and in vivo, facilitating the recruitment of cytotoxic CD4+T cells (CD4+CTL) expressing CD4+, NKG2D+, CRTAM+, and Perforin+. Lung_cancer Inhibiting_target_recognition 660 KLRK1 38609101 Lung cancer lung cancer Inhibiting target recognition Very interestingly, our findings also revealed that QAPHA upregulated major histocompatibility complex class II (MHC-II) expression on TC-1 tumor cells both in vitro and in vivo, facilitating the recruitment of cytotoxic CD4+T cells (CD4+CTL) expressing CD4+, NKG2D+, CRTAM+, and Perforin+. Lung_cancer Inhibiting_target_recognition 661 CRTAM 38609101 Lung cancer lung cancer Inhibiting target recognition Very interestingly, our findings also revealed that QAPHA upregulated major histocompatibility complex class II (MHC-II) expression on TC-1 tumor cells both in vitro and in vivo, facilitating the recruitment of cytotoxic CD4+T cells (CD4+CTL) expressing CD4+, NKG2D+, CRTAM+, and Perforin+. Lung_cancer Inhibiting_target_recognition 662 PRF1 38609101 Lung cancer lung cancer Inhibiting target recognition Very interestingly, our findings also revealed that QAPHA upregulated major histocompatibility complex class II (MHC-II) expression on TC-1 tumor cells both in vitro and in vivo, facilitating the recruitment of cytotoxic CD4+T cells (CD4+CTL) expressing CD4+, NKG2D+, CRTAM+, and Perforin+. Lung_cancer Inhibiting_target_recognition 663 HLA-DMA 38600469 Gastrointestinal cancer gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Gastrointestinal_cancer Inhibiting_target_recognition 664 HLA-DMA 38600469 Melanoma gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Melanoma Inhibiting_target_recognition 665 HLA-DMB 38600469 Gastrointestinal cancer gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Gastrointestinal_cancer Inhibiting_target_recognition 666 HLA-DMB 38600469 Melanoma gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Melanoma Inhibiting_target_recognition 667 HLA-DOA 38600469 Gastrointestinal cancer gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Gastrointestinal_cancer Inhibiting_target_recognition 668 HLA-DOA 38600469 Melanoma gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Melanoma Inhibiting_target_recognition 669 HLA-DOB 38600469 Gastrointestinal cancer gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Gastrointestinal_cancer Inhibiting_target_recognition 670 HLA-DOB 38600469 Melanoma gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Melanoma Inhibiting_target_recognition 671 PCSK9 38600469 Gastrointestinal cancer gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Gastrointestinal_cancer Inhibiting_target_recognition 672 PCSK9 38600469 Melanoma gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Melanoma Inhibiting_target_recognition 673 CD8A 38600469 Gastrointestinal cancer gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Gastrointestinal_cancer Inhibiting_target_recognition 674 CD8A 38600469 Melanoma gastric cancer and melanoma Inhibiting target recognition Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Melanoma Inhibiting_target_recognition 675 EZH2 38315170 Melanoma melanoma Inhibiting target recognition Notably, targeted inhibition assays revealed that inhibition of EZH2 influences the expression dynamics and inducibility of the MHC-II pathway following IFN-γ stimulation. Melanoma Inhibiting_target_recognition 676 IFNG 38315170 Melanoma melanoma Inhibiting target recognition Notably, targeted inhibition assays revealed that inhibition of EZH2 influences the expression dynamics and inducibility of the MHC-II pathway following IFN-γ stimulation. Melanoma Inhibiting_target_recognition 677 ROCK1 38199985 Melanoma melanoma Inhibiting target recognition Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1β, iNOS and TNF production in myeloid cells. Melanoma Inhibiting_target_recognition 678 ROCK2 38199985 Melanoma melanoma Inhibiting target recognition Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1β, iNOS and TNF production in myeloid cells. Melanoma Inhibiting_target_recognition 679 KDR 37438548 Breast cancer breast cancer Inhibiting target recognition Our results showed that VEGFR2-targeting CAR-Ms could be activated under the stimulation of VEGFR2-expressing cells. They exhibited higher expression of CD86, MHCII and TNF-α in vitro and enhanced tumor suppressive abilities in vivo. Breast_cancer Inhibiting_target_recognition 680 MAT1A 37236192 Breast cancer breast cancer Inhibiting target recognition By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Breast_cancer Inhibiting_target_recognition 681 FASN 37236192 Breast cancer breast cancer Inhibiting target recognition By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Breast_cancer Inhibiting_target_recognition 682 HLA-DMA 37236192 Breast cancer breast cancer Inhibiting target recognition By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Breast_cancer Inhibiting_target_recognition 683 HLA-DMB 37236192 Breast cancer breast cancer Inhibiting target recognition By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Breast_cancer Inhibiting_target_recognition 684 HLA-DOA 37236192 Breast cancer breast cancer Inhibiting target recognition By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Breast_cancer Inhibiting_target_recognition 685 HLA-DOB 37236192 Breast cancer breast cancer Inhibiting target recognition By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Breast_cancer Inhibiting_target_recognition 686 IL15 37071397 Melanoma melanoma Inhibiting target recognition We found increased expression of IL15 and MHC-II in murine melanoma cells upon p53 induction by MDM2-inhibition. MDM2-inhibitor induced MHC-II and IL15-production, which was p53 dependent as Tp53 knockdown blocked the effect. Melanoma Inhibiting_target_recognition 687 TP53 37071397 Melanoma melanoma Inhibiting target recognition We found increased expression of IL15 and MHC-II in murine melanoma cells upon p53 induction by MDM2-inhibition. MDM2-inhibitor induced MHC-II and IL15-production, which was p53 dependent as Tp53 knockdown blocked the effect. Melanoma Inhibiting_target_recognition 688 MDM2 37071397 Melanoma melanoma Inhibiting target recognition We found increased expression of IL15 and MHC-II in murine melanoma cells upon p53 induction by MDM2-inhibition. MDM2-inhibitor induced MHC-II and IL15-production, which was p53 dependent as Tp53 knockdown blocked the effect. Melanoma Inhibiting_target_recognition 689 CD276 36869048 Renal cancer renal cancer, lung cancer, breast cancer, prostate cancer Inhibiting target recognition Inhibition of B7-H3 suppresses mTORC1-hyperactive tumor growth via an immune-mediated mechanism involving increased T-cell activity and IFN-γ responses coupled with increased tumor cell expression of MHC-II. Renal_cancer Inhibiting_target_recognition 690 CD276 36869048 Lung cancer renal cancer, lung cancer, breast cancer, prostate cancer Inhibiting target recognition Inhibition of B7-H3 suppresses mTORC1-hyperactive tumor growth via an immune-mediated mechanism involving increased T-cell activity and IFN-γ responses coupled with increased tumor cell expression of MHC-II. Lung_cancer Inhibiting_target_recognition 691 CD276 36869048 Breast cancer renal cancer, lung cancer, breast cancer, prostate cancer Inhibiting target recognition Inhibition of B7-H3 suppresses mTORC1-hyperactive tumor growth via an immune-mediated mechanism involving increased T-cell activity and IFN-γ responses coupled with increased tumor cell expression of MHC-II. Breast_cancer Inhibiting_target_recognition 692 CD276 36869048 Prostate cancer renal cancer, lung cancer, breast cancer, prostate cancer Inhibiting target recognition Inhibition of B7-H3 suppresses mTORC1-hyperactive tumor growth via an immune-mediated mechanism involving increased T-cell activity and IFN-γ responses coupled with increased tumor cell expression of MHC-II. Prostate_cancer Inhibiting_target_recognition 693 MDM2 35853161 Leukemia acute myeloid leukemia Inhibiting target recognition MDM2 inhibition induced MHC class I and II expression in murine and human AML cells. Using xenografts of human AML and syngeneic mouse models of leukemia, we show that MDM2 inhibition enhanced cytotoxicity against leukemia cells and improved survival. Leukemia Inhibiting_target_recognition 694 TRIM22 35777501 Brain cancer glioblastoma Inhibiting target recognition We showed that inhibition of TRIM22 can increase the amount of MHC-II expression in cancer cells, suggesting a possibility of providing the biological basis for a possible therapeutic target to potentiate checkpoint blockade immunotherapy. Brain_cancer Inhibiting_target_recognition 695 TFEB 35504056 Lung cancer lung cancer Inhibiting target recognition TFEB knockdown significantly promoted the differentiation and maturation of TEDCs, with upregulated expression of CD11c and costimulatory molecules (CD86 and MHC-II) but reduced expression of the inhibitory molecule PD-L1, and enhanced their ability to induce Th1 proliferation and differentiation. Lung_cancer Inhibiting_target_recognition 696 YTHDF1 35193930 Gastrointestinal cancer gastric tumors Inhibiting target recognition Consistently, YTHDF1 loss in GC tumors led to recruitment of mature dendritic cells (DCs) with increased MHCII expression and interleukin-12 (IL-12) secretion, which in turn, promoted CD4+ and CD8+ T cells infiltration with increased interferon-γ (IFN-γ) secretion. Gastrointestinal_cancer Inhibiting_target_recognition 697 IFNG 35193930 Gastrointestinal cancer gastric tumors Inhibiting target recognition Consistently, YTHDF1 loss in GC tumors led to recruitment of mature dendritic cells (DCs) with increased MHCII expression and interleukin-12 (IL-12) secretion, which in turn, promoted CD4+ and CD8+ T cells infiltration with increased interferon-γ (IFN-γ) secretion. Gastrointestinal_cancer Inhibiting_target_recognition 698 HSPA4 34552825 Pancreatic cancer pancreatic cancer Inhibiting target recognition Hsp70-/- dendritic cells showed increased expression of MHCII and TNF-α both in vitro and in vivo. These results suggest that the absence of Hsp70 in the TME inhibits tumors through increased dendritic cell activation. Hsp70 inhibition in DCs may emerge as a novel therapeutic strategy against pancreatic cancer. Pancreatic_cancer Inhibiting_target_recognition 699 SUGT1 33271120 Lymphoma lymphoma Inhibiting target recognition We established SUGT1 as a major positive regulator of both MHC-I and MHC-II cell surface expression. Further, pharmacological inhibition of two negative regulators of antigen presentation, EZH2 and thymidylate synthase, enhanced DLBCL MHC-I presentation. Lymphoma Inhibiting_target_recognition 700 EZH2 33271120 Lymphoma lymphoma Inhibiting target recognition We established SUGT1 as a major positive regulator of both MHC-I and MHC-II cell surface expression. Further, pharmacological inhibition of two negative regulators of antigen presentation, EZH2 and thymidylate synthase, enhanced DLBCL MHC-I presentation. Lymphoma Inhibiting_target_recognition 701 TYMS 33271120 Lymphoma lymphoma Inhibiting target recognition We established SUGT1 as a major positive regulator of both MHC-I and MHC-II cell surface expression. Further, pharmacological inhibition of two negative regulators of antigen presentation, EZH2 and thymidylate synthase, enhanced DLBCL MHC-I presentation. Lymphoma Inhibiting_target_recognition 702 MYOZ3 31904453 liver cancer liver cancer Inhibiting target recognition The CS3-adjuvanted DC vaccine increased CD80, MHC-I and MHC-II expression, promoted CD8+ T cell infiltration, upregulated TNF-α and IFN-γ transcription, and downregulated TGF-β transcription in tumor tissues. liver_cancer Inhibiting_target_recognition 703 PIK3CB 31548239 Head and neck cancer head and neck squamous cell carcinoma Inhibiting target recognition Collectively, these findings demonstrate that MHC expression can be modulated by PI3K signaling and suggest that activation of PI3K signaling may promote immune escape via effects on antigen presentation. Head_and_neck_cancer Inhibiting_target_recognition 704 PIK3CA 31548239 Head and neck cancer head and neck squamous cell carcinoma Inhibiting target recognition Collectively, these findings demonstrate that MHC expression can be modulated by PI3K signaling and suggest that activation of PI3K signaling may promote immune escape via effects on antigen presentation. Head_and_neck_cancer Inhibiting_target_recognition 705 PIK3CG 31548239 Head and neck cancer head and neck squamous cell carcinoma Inhibiting target recognition Collectively, these findings demonstrate that MHC expression can be modulated by PI3K signaling and suggest that activation of PI3K signaling may promote immune escape via effects on antigen presentation. Head_and_neck_cancer Inhibiting_target_recognition 706 PIK3CD 31548239 Head and neck cancer head and neck squamous cell carcinoma Inhibiting target recognition Collectively, these findings demonstrate that MHC expression can be modulated by PI3K signaling and suggest that activation of PI3K signaling may promote immune escape via effects on antigen presentation. Head_and_neck_cancer Inhibiting_target_recognition 707 NUDT21 38349866 Pan-cancer pan-cancer Inhibiting target recognition Based on the pan-cancer analysis, we found that elevated expression of NUDT21 in most cancers was significantly correlated with TMB, MSI, neoantigens and chromosomal ploidy, and in epigenetics, elevated NUDT21 expression was strongly associated with genomic stability, mismatch repair genes, tumor stemness, and RNA methylation. Based on immunosuppressive score, we found that NUDT21 plays anessential role in the immunosuppressive environment by suppressing immune checkpointing effect in most cancers. Pan-cancer Inhibiting_target_recognition 708 CHAF1A 38235318 Gastrointestinal cancer gastric cancer Inhibiting target recognition High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigenburden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. Gastrointestinal_cancer Inhibiting_target_recognition 709 TRDV1 38172341 Melanoma melanoma Inhibiting target recognition Here we demonstrate that intratumoral TRDV1 transcripts (encoding the TCRδ chain of Vδ1+ γδ T cells) predict anti-PD-1 CPI response in patients with melanoma, particularly those harboring below average neoantigens. Melanoma Inhibiting_target_recognition 710 PRMT1 38125466 Lung cancer lung adenocarcinoma Inhibiting target recognition Our study ultimately revealed that the inhibition of PRMT1 and PRMT5 in lung adenocarcinoma resulted in the activation of the cGAS-STING pathway, especially after radiation. It was also found that the expression of PRMT1 and PRMT5 influenced proliferation, migration, and invasion of human lung adenocarcinoma cell lines. Lung_cancer Inhibiting_target_recognition 711 PRMT5 38125466 Lung cancer lung adenocarcinoma Inhibiting target recognition Our study ultimately revealed that the inhibition of PRMT1 and PRMT5 in lung adenocarcinoma resulted in the activation of the cGAS-STING pathway, especially after radiation. It was also found that the expression of PRMT1 and PRMT6 influenced proliferation, migration, and invasion of human lung adenocarcinoma cell lines. Lung_cancer Inhibiting_target_recognition 712 CGAS 38125466 Lung cancer lung adenocarcinoma Inhibiting target recognition Our study ultimately revealed that the inhibition of PRMT1 and PRMT5 in lung adenocarcinoma resulted in the activation of the cGAS-STING pathway, especially after radiation. It was also found that the expression of PRMT1 and PRMT7 influenced proliferation, migration, and invasion of human lung adenocarcinoma cell lines. Lung_cancer Inhibiting_target_recognition 713 STING1 38125466 Lung cancer lung adenocarcinoma Inhibiting target recognition Our study ultimately revealed that the inhibition of PRMT1 and PRMT5 in lung adenocarcinoma resulted in the activation of the cGAS-STING pathway, especially after radiation. It was also found that the expression of PRMT1 and PRMT8 influenced proliferation, migration, and invasion of human lung adenocarcinoma cell lines. Lung_cancer Inhibiting_target_recognition 714 DLL3 37731022 Lung cancer small-cell lung cancer Inhibiting target recognition Although SCLC with DLL3High had a higher neoantigen load, these tumors were resistant to immunochemotherapy due to suppressed tumor immunity by inhibiting antigen-presenting functions. Lung_cancer Inhibiting_target_recognition 715 TP53 37602328 Pan-cancer review, pan-cancer Inhibiting target recognition In some contexts, p53 mutations increase neoantigen load which improves response to immune checkpoint inhibition. Therapeutic restoration of mutated p53 can restore anti-cancer immune cell infiltration and ameliorate pro-tumor signaling to induce tumor regression. Pan-cancer Inhibiting_target_recognition 716 SHOX2 37170390 Brain cancer glioma Inhibiting target recognition Immune analysis showed that SHOX2 was closely correlated with the tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen and neoantigens and immune checkpoint (ICP) in a variety of tumors and could influence the immunotherapy sensitivity of cancers. Brain_cancer Inhibiting_target_recognition 717 OIP5 36819584 Lung cancer lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma Inhibiting target recognition High OIP5 expression was related to immune regulation and neoantigen production, particularly in terms of the levels of immune regulatory molecules and the number of neoantigens produced in lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma. Lung_cancer Inhibiting_target_recognition 718 OIP5 36819584 Other cancers lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma Inhibiting target recognition High OIP5 expression was related to immune regulation and neoantigen production, particularly in terms of the levels of immune regulatory molecules and the number of neoantigens produced in lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma. Other_cancers Inhibiting_target_recognition 719 OIP5 36819584 Breast cancer lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma Inhibiting target recognition High OIP5 expression was related to immune regulation and neoantigen production, particularly in terms of the levels of immune regulatory molecules and the number of neoantigens produced in lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma. Breast_cancer Inhibiting_target_recognition 720 OIP5 36819584 Gastrointestinal cancer lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma Inhibiting target recognition High OIP5 expression was related to immune regulation and neoantigen production, particularly in terms of the levels of immune regulatory molecules and the number of neoantigens produced in lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma. Gastrointestinal_cancer Inhibiting_target_recognition 721 OIP5 36819584 Brain cancer lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma Inhibiting target recognition High OIP5 expression was related to immune regulation and neoantigen production, particularly in terms of the levels of immune regulatory molecules and the number of neoantigens produced in lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma. Brain_cancer Inhibiting_target_recognition 722 OIP5 36819584 Prostate cancer lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma Inhibiting target recognition High OIP5 expression was related to immune regulation and neoantigen production, particularly in terms of the levels of immune regulatory molecules and the number of neoantigens produced in lung adenocarcinoma, uterine corpus endometrial carcinoma, breast cancer, stomach adenocarcinoma, low-grade glioma, and prostate adenocarcinoma. Prostate_cancer Inhibiting_target_recognition 723 NT5E 36628293 Breast cancer breast cancer Inhibiting target recognition Cancer cells evade the immune system by expressing inhibitory immune checkpoint receptors such as ecto-5'-nucleotidase (NT5E), also known as CD73, which consequently suppress tumor neoantigen-specific immune response. Breast_cancer Inhibiting_target_recognition 724 IL6 36443756 Breast cancer breast, lung and pancreatic cancer Inhibiting target recognition IL-6/STAT3 signaling induces SMG1, which limits the expression of potent frameshift neoantigens that are under NMD control compromising the outcome of the immune response. Breast_cancer Inhibiting_target_recognition 725 IL6 36443756 Lung cancer breast, lung and pancreatic cancer Inhibiting target recognition IL-6/STAT3 signaling induces SMG1, which limits the expression of potent frameshift neoantigens that are under NMD control compromising the outcome of the immune response. Lung_cancer Inhibiting_target_recognition 726 IL6 36443756 Pancreatic cancer breast, lung and pancreatic cancer Inhibiting target recognition IL-6/STAT3 signaling induces SMG1, which limits the expression of potent frameshift neoantigens that are under NMD control compromising the outcome of the immune response. Pancreatic_cancer Inhibiting_target_recognition 727 STAT3 36443756 Breast cancer breast, lung and pancreatic cancer Inhibiting target recognition IL-6/STAT3 signaling induces SMG2, which limits the expression of potent frameshift neoantigens that are under NMD control compromising the outcome of the immune response. Breast_cancer Inhibiting_target_recognition 728 STAT3 36443756 Lung cancer breast, lung and pancreatic cancer Inhibiting target recognition IL-6/STAT3 signaling induces SMG2, which limits the expression of potent frameshift neoantigens that are under NMD control compromising the outcome of the immune response. Lung_cancer Inhibiting_target_recognition 729 STAT3 36443756 Pancreatic cancer breast, lung and pancreatic cancer Inhibiting target recognition IL-6/STAT3 signaling induces SMG2, which limits the expression of potent frameshift neoantigens that are under NMD control compromising the outcome of the immune response. Pancreatic_cancer Inhibiting_target_recognition 730 SMG1 36443756 Breast cancer breast, lung and pancreatic cancer Inhibiting target recognition IL-6/STAT3 signaling induces SMG3, which limits the expression of potent frameshift neoantigens that are under NMD control compromising the outcome of the immune response. Breast_cancer Inhibiting_target_recognition 731 SMG1 36443756 Lung cancer breast, lung and pancreatic cancer Inhibiting target recognition IL-6/STAT3 signaling induces SMG3, which limits the expression of potent frameshift neoantigens that are under NMD control compromising the outcome of the immune response. Lung_cancer Inhibiting_target_recognition 732 SMG1 36443756 Pancreatic cancer breast, lung and pancreatic cancer Inhibiting target recognition IL-6/STAT3 signaling induces SMG3, which limits the expression of potent frameshift neoantigens that are under NMD control compromising the outcome of the immune response. Pancreatic_cancer Inhibiting_target_recognition 733 DPY30 36185638 Melanoma melanoma Inhibiting target recognition The mRNA level of DPY30 in melanoma was higher than in normal tissues. The expression of DPY30 was positively associated with TMB, neoantigens and PD-L1 expression. Melanoma Inhibiting_target_recognition 734 CISH 36007524 Melanoma melanoma Inhibiting target recognition CISH deletion using CRISPR/Cas9 resulted in hyper-activation and improved functional avidity against tumor-derived neoantigens without perturbing T cell maturation. Cish knockout resulted in increased susceptibility to checkpoint blockade in vivo. Melanoma Inhibiting_target_recognition 735 SMARCA2 35992833 Breast cancer breast cancer Inhibiting target recognition BrM harbored higher mutational burden and SNV-derived neoantigen expression along with reduced immune gene signature expression relative to primary TNBC. Immune signatures correlated with improved survival, including T cell signatures. Breast_cancer Inhibiting_target_recognition 736 VSIR 35493077 Pan-cancer pan-cancer Inhibiting target recognition Elevated VSIR was closely correlated with infiltrated inflammatory cells, neoantigens expression, MSI, TMB, and classical immune checkpoints in the tumor microenvironment. Pan-cancer Inhibiting_target_recognition 737 BSG 35464411 Pan-cancer pan-cancer Inhibiting target recognition CD147 expression exhibited a strong association with immune infiltrates, immune checkpoint molecules, and neoantigen levels in the tumor microenvironment. Pan-cancer Inhibiting_target_recognition 738 CSF1R 35444953 Colon cancer colon adenocarcinoma Inhibiting target recognition CSF-1R was significantly correlated with TME, immune cell infiltration, TMB, MSI, Neoantigen, and immune checkpoint molecules. Colon_cancer Inhibiting_target_recognition 739 KMT2C 35345335 Melanoma melanoma Inhibiting target recognition Although KMT2C mutation has no significant influence on immune cell infiltration into MM tumors, the tumor mutation load and neoantigen load are indeed elevated in KMT2C mutated MM samples. Melanoma Inhibiting_target_recognition 740 HLA-A 35299174 gastrointestinal cancer gastrointestinal cancer Inhibiting target recognition Recurrent somatic mutations of the HLA-Ⅰand B2M, which constitute the antigen presentation machinery, have been reported in GI cancers. gastrointestinal_cancer Inhibiting_target_recognition 741 HLA-B 35299174 gastrointestinal cancer gastrointestinal cancer Inhibiting target recognition Recurrent somatic mutations of the HLA-Ⅰand B2M, which constitute the antigen presentation machinery, have been reported in GI cancers. gastrointestinal_cancer Inhibiting_target_recognition 742 HLA-C 35299174 gastrointestinal cancer gastrointestinal cancer Inhibiting target recognition Recurrent somatic mutations of the HLA-Ⅰand B2M, which constitute the antigen presentation machinery, have been reported in GI cancers. gastrointestinal_cancer Inhibiting_target_recognition 743 B2M 35299174 gastrointestinal cancer gastrointestinal cancer Inhibiting target recognition Recurrent somatic mutations of the HLA-Ⅰand B2M, which constitute the antigen presentation machinery, have been reported in GI cancers. gastrointestinal_cancer Inhibiting_target_recognition 744 GPM6A 35035657 Lung cancer lung cancer Inhibiting target recognition Increased neoantigen burden was also linked to a high m6A score. Patients with a higher m6A score saw substantial therapeutic and clinical improvements. Lung_cancer Inhibiting_target_recognition 745 TAP1 34957213 Ovarian cancer ovarian cancer Inhibiting target recognition TAP1 was correlated with immune checkpoint genes, DNA methylation, tumor mutation burden, microsatellite instability, and neoantigens in various cancers. Our results showed that TAP1 was upregulated in ovarian cancer cell lines and was associated with poor prognosis. Ovarian_cancer Inhibiting_target_recognition 746 PTPA 34911954 Colon cancer colorectal cancer, triple-negative breast cancer and pancreatic cancer Inhibiting target recognition In mouse models of MSS and MSI colorectal cancers, triple-negative breast cancer and pancreatic cancer, PP2A inhibition triggers neoantigen production, cytotoxic T cell infiltration and ICB sensitization. Colon_cancer Inhibiting_target_recognition 747 PTPA 34911954 Breast cancer colorectal cancer, triple-negative breast cancer and pancreatic cancer Inhibiting target recognition In mouse models of MSS and MSI colorectal cancers, triple-negative breast cancer and pancreatic cancer, PP2A inhibition triggers neoantigen production, cytotoxic T cell infiltration and ICB sensitization. Breast_cancer Inhibiting_target_recognition 748 PTPA 34911954 Pancreatic cancer colorectal cancer, triple-negative breast cancer and pancreatic cancer Inhibiting target recognition In mouse models of MSS and MSI colorectal cancers, triple-negative breast cancer and pancreatic cancer, PP2A inhibition triggers neoantigen production, cytotoxic T cell infiltration and ICB sensitization. Pancreatic_cancer Inhibiting_target_recognition 749 CD47 34858730 Pan-cancer pan-cancer Inhibiting target recognition Cancer cells exploit CD47 overexpression to inhibit phagocytic elimination and neoantigen processing via the myeloid CD47-SIRPα axis and thereby indirectly evade adaptive T cell immunity. Pan-cancer Inhibiting_target_recognition 750 PDCD1 34290408 Lung cancer non-small cell lung cancer Inhibiting target recognition PD-1 blockade unleashes CD8 T cells1, including those specific for mutation-associated neoantigens (MANA)。 Lung_cancer Inhibiting_target_recognition 751 MYCN 33932141 Renal cancer Wilms' tumor and Neuroblastoma Inhibiting target recognition For neuroblastomas, the cases with higher levels of neoantigens were confined to the group without MYCN-amplification and for Wilms tumor restricted to the TP53-mutated cases. Renal_cancer Inhibiting_target_recognition 752 MYCN 33932141 Other cancers Wilms' tumor and Neuroblastoma Inhibiting target recognition For neuroblastomas, the cases with higher levels of neoantigens were confined to the group without MYCN-amplification and for Wilms tumor restricted to the TP53-mutated cases. Other_cancers Inhibiting_target_recognition 753 TP53 33932141 Renal cancer Wilms' tumor and Neuroblastoma Inhibiting target recognition For neuroblastomas, the cases with higher levels of neoantigens were confined to the group without MYCN-amplification and for Wilms tumor restricted to the TP53-mutated cases. Renal_cancer Inhibiting_target_recognition 754 TP53 33932141 Other cancers Wilms' tumor and Neuroblastoma Inhibiting target recognition For neuroblastomas, the cases with higher levels of neoantigens were confined to the group without MYCN-amplification and for Wilms tumor restricted to the TP53-mutated cases. Other_cancers Inhibiting_target_recognition 755 TP53 33356494 Bladder cancer bladder cancer Inhibiting target recognition The patients with TP53-MT showed stronger tumor antigenicity and tumor antigen presentation, as indicated by a higher tumor mutational load, a higher neoantigen load and increased expression of MHC. Bladder_cancer Inhibiting_target_recognition 756 PDCD1 32729901 Colon cancer colorectal cancer and melanoma Inhibiting target recognition Accordingly, newly emerged tumor neoantigen-specific CD8+ T cells with enhanced effector functions were significantly increased in mice treated with PD-1/PD-L1 blockade. Colon_cancer Inhibiting_target_recognition 757 PDCD1 32729901 Melanoma colorectal cancer and melanoma Inhibiting target recognition Accordingly, newly emerged tumor neoantigen-specific CD8+ T cells with enhanced effector functions were significantly increased in mice treated with PD-1/PD-L1 blockade. Melanoma Inhibiting_target_recognition 758 CD274 32729901 Colon cancer colorectal cancer and melanoma Inhibiting target recognition Accordingly, newly emerged tumor neoantigen-specific CD8+ T cells with enhanced effector functions were significantly increased in mice treated with PD-1/PD-L1 blockade. Colon_cancer Inhibiting_target_recognition 759 CD274 32729901 Melanoma colorectal cancer and melanoma Inhibiting target recognition Accordingly, newly emerged tumor neoantigen-specific CD8+ T cells with enhanced effector functions were significantly increased in mice treated with PD-1/PD-L1 blockade. Melanoma Inhibiting_target_recognition 760 STING1 32701257 Colon cancer colon adenocarcinoma Inhibiting target recognition The stimulator of interferon genes (STING) pathway is an endogenous mechanism by which the innate immune system generates an immunological context for priming and mobilizing neoantigen-specific T cells. Colon_cancer Inhibiting_target_recognition 761 PARP1 30791940 Other cancers urothelial bladder cancer Inhibiting target recognition PARP inhibition, by amplifying the DNA damage, augments the mutational burden and promotes the immune priming of the tumor by increasing the neoantigen exposure and determining upregulation of programmed death ligand 1 (PD-L1) expression. Other_cancers Inhibiting_target_recognition 762 GPM6A 30728504 Colon cancer colon adenocarcinoma and melanoma Inhibiting target recognition Here we show that durable neoantigen-specific immunity is regulated by mRNA N6-methyadenosine (m6A) methylation through the m6A-binding protein YTHDF1. Colon_cancer Inhibiting_target_recognition 763 GPM6A 30728504 Melanoma colon adenocarcinoma and melanoma Inhibiting target recognition Here we show that durable neoantigen-specific immunity is regulated by mRNA N6-methyadenosine (m6A) methylation through the m6A-binding protein YTHDF1. Melanoma Inhibiting_target_recognition 764 YTHDF1 30728504 Colon cancer colon adenocarcinoma and melanoma Inhibiting target recognition Here we show that durable neoantigen-specific immunity is regulated by mRNA N6-methyadenosine (m6A) methylation through the m6A-binding protein YTHDF1. Colon_cancer Inhibiting_target_recognition 765 YTHDF1 30728504 Melanoma colon adenocarcinoma and melanoma Inhibiting target recognition Here we show that durable neoantigen-specific immunity is regulated by mRNA N6-methyadenosine (m6A) methylation through the m6A-binding protein YTHDF1. Melanoma Inhibiting_target_recognition 766 TUBA1B 38589634 Pan-cancer pan-cancer Inhibiting target recognition TUBA1B's expression impacted some cancers by elevating tumor mutation burden, microsatellite instability, neoantigen formation, immune cell infiltration, and the modulation of immune checkpoints. Pan-cancer Inhibiting_target_recognition 767 COTL1 38523681 Pan-cancer pan-cancer Inhibiting target recognition COTL1 was also linked to tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1), all of which are potential targets for immunotherapies. Pan-cancer Inhibiting_target_recognition 768 ANK3 38482441 Pan-cancer pan-cancer Inhibiting target recognition ANK3 was also associated with ICs, immune neoantigens, MSI, the tumor mutation load, MMR genes, and DNA methylation. Pan-cancer Inhibiting_target_recognition 769 ATR 38474014 Pan-cancer review, pan-cancer Inhibiting target recognition ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Pan-cancer Inhibiting_target_recognition 770 CGAS 38474014 Pan-cancer review, pan-cancer Inhibiting target recognition ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Pan-cancer Inhibiting_target_recognition 771 STING1 38474014 Pan-cancer review, pan-cancer Inhibiting target recognition ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Pan-cancer Inhibiting_target_recognition 772 POLQ 38457207 Bladder cancer bladder cancer Inhibiting target recognition Further analysis revealed that high POLQ expression was linked to chromosome instability and higher tumor mutational burden (TMB), which might elicit the production of neoantigens. Further, high POLQ expression was associated with an active tumor immune microenvironment with abundant infiltration of immune effector cells and molecules. Bladder_cancer Inhibiting_target_recognition 773 RB1 38383412 Lung cancer small-cell lung carcinoma Inhibiting target recognition Intriguingly, RB1 inactivation emerged as a factor influencing TIME heterogeneity in cSCLC, possibly through neoantigen depletion. Lung_cancer Inhibiting_target_recognition 774 LRP1B 38381429 Colon cancer rectal cancer Inhibiting target recognition Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Colon_cancer Inhibiting_target_recognition 775 NFIL3 38356719 Ovarian cancer ovarian cancer Inhibiting target recognition Notably, NFIL3 expression demonstrated a robust correlation with several pivotal aspects, including prognosis, immune cell infiltration, immune checkpoint-related genes, TMB, MSI, tumor purity, and the presence of neoantigens. Ovarian_cancer Inhibiting_target_recognition 776 PTPRT 38216925 Lung cancer non-small cell lung cancer Inhibiting target recognition PTPRT downregulation was associated with elevated tumour mutation burden and tumour neoantigen burden in lung cancer, indicating the potential influence on tumour immunogenicity. Lung_cancer Inhibiting_target_recognition 777 ARID1A 38148578 Gastrointestinal cancer gastric cancer Inhibiting target recognition ARID1A-loss tumors demonstrated elevated mutation burden, neoantigen load, and interferon gamma pathway activation. Gastrointestinal_cancer Inhibiting_target_recognition 778 NOTCH4 35967450 Melanoma melanoma Inhibiting target recognition Further exploration found that NOTCH4-Mut tumors had higher tumor mutation burden (TMB) and tumor neoantigen burden (TNB) (P <0.05). Melanoma Inhibiting_target_recognition 779 SNHG1 35592519 Liver cancer Hepatocellular carcinoma Inhibiting target recognition In addition, lower tumor neoantigen burden was observed in high SNHG1 or SNHG3 group. Liver_cancer Inhibiting_target_recognition 780 SNHG3 35592519 Liver cancer Hepatocellular carcinoma Inhibiting target recognition In addition, lower tumor neoantigen burden was observed in high SNHG1 or SNHG3 group. Liver_cancer Inhibiting_target_recognition 781 CXCR3 35562800 Other cancers urothelial carcinoma Inhibiting target recognition Immunogenicity analysis showed the CXCR3-high group had higher tumor neoantigen burden (TNB). Our study suggests that CXCR3 pathway activation may be a novel predictive biomarker for the effectiveness of immunotherapy in mUC patients. Other_cancers Inhibiting_target_recognition 782 KDR 35530271 Pan-cancer pan-cancer Inhibiting target recognition KDR mutation was associated with tumor mutation burden high, neoantigen burden and immune cellular activities. Pan-cancer Inhibiting_target_recognition 783 ERBB2 35281032 Pan-cancer pan-cancer Inhibiting target recognition HER2 mutation was not associated with HER2 protein expression but was positively associated with microsatellite instability, tumor mutation and neoantigen burdens, infiltrating antitumor immune cells, and signal activities of antitumor immunity. Pan-cancer Inhibiting_target_recognition 784 CCL4 32332013 Melanoma melanoma Inhibiting recruitment of dendritic cells In support of this, melanoma cell intrinsic secretion of CCL4 can attract cDC1, although this can be blocked by activated β-catenin signaling. Studies of hepatocellular carcinoma have also connected the β-catenin pathway with cDC1 tumor infiltration and anti-PD-1 response. Melanoma Inhibiting_recruitment_of_dendritic_cells 785 CTNNB1 32332013 Liver cancer hepatocellular carcinoma Inhibiting recruitment of dendritic cells In support of this, melanoma cell intrinsic secretion of CCL4 can attract cDC1, although this can be blocked by activated β-catenin signaling. Studies of hepatocellular carcinoma have also connected the β-catenin pathway with cDC1 tumor infiltration and anti-PD-1 response. Liver_cancer Inhibiting_recruitment_of_dendritic_cells 786 CCL5 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells Other mechanisms also likely influence cDC1 recruitment noting that NK cells are primary producers of the cDC1 attractive chemokines CCL5 and XCL1, and the DC differentiation factor Flt3L. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 787 STING1 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cGAMP then functions as a second messenger and binds STING to activate downstream signaling. This triggers interferon response genes and the production of CCL5, which can attract cDC1s. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 788 CGAS 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells Extracellular tumor DNA, or cGAMP can activate tumor DCs and initiate T cell responses in the draining lymph node. Tumor cell loss of LKB1 is associated with poor T cell infiltration and non-response to ICB therapy, and correspondingly STING signaling pathways can be inhibited by LKB1 loss. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 789 XCL1 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells Other mechanisms also likely influence cDC1 recruitment noting that NK cells are primary producers of the cDC1 attractive chemokines CCL5 and XCL1, and the DC differentiation factor Flt3L. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 790 FLT3LG 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells Other mechanisms also likely influence cDC1 recruitment noting that NK cells are primary producers of the cDC1 attractive chemokines CCL5 and XCL1, and the DC differentiation factor Flt3L. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 791 CCL5 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cGAMP then functions as a second messenger and binds STING to activate downstream signaling. This triggers interferon response genes and the production of CCL5, which can attract cDC1s. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 792 CGAS 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cGAMP then functions as a second messenger and binds STING to activate downstream signaling. This triggers interferon response genes and the production of CCL5, which can attract cDC1s. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 793 PTGES2 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells Tumor cell derived prostaglandin E2 (PGE2) can inhibit both NK and cDC1 recruitment, leading to a non-T cell-inflamed tumor microenvironment. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 794 RIGI 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells In this setting, tumor intrinsic type I interferon production is independent of RIG-I, another cytosolic dsRNA sensor, however tumor cell intrinsic RIG-I has been implicated in anti-CTLA-4 response, and combining anti-CTLA-4 with RIG-I agonist could enhance anti-tumor responses through cDC1 cross-presentation of tumor antigens. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 795 CTLA4 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells In this setting, tumor intrinsic type I interferon production is independent of RIG-I, another cytosolic dsRNA sensor, however tumor cell intrinsic RIG-I has been implicated in anti-CTLA-4 response, and combining anti-CTLA-4 with RIG-I agonist could enhance anti-tumor responses through cDC1 cross-presentation of tumor antigens. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 796 IFNG 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells T cell-derived interferon γ inhibits tumor cell growth and activates local tumor cDC1 to produce IL-12, and the chemokines CXCL9 and CXCL10. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 797 IL12B 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells T cell-derived interferon γ inhibits tumor cell growth and activates local tumor cDC1 to produce IL-12, and the chemokines CXCL9 and CXCL10. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 798 IL12A 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells T cell-derived interferon γ inhibits tumor cell growth and activates local tumor cDC1 to produce IL-12, and the chemokines CXCL9 and CXCL10. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 799 CXCL9 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells T cell-derived interferon γ inhibits tumor cell growth and activates local tumor cDC1 to produce IL-12, and the chemokines CXCL9 and CXCL10. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 800 CXCL10 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells T cell-derived interferon γ inhibits tumor cell growth and activates local tumor cDC1 to produce IL-12, and the chemokines CXCL9 and CXCL10. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 801 BATF3 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells Beyond the association of DCs and the T cell-inflamed tumor microenvironment, the presence of the Batf3 transcription factor within DCs is becoming apparent as a necessary condition for anti-cancer immunity. This has been emphasized by Batf3 murine knockout systems which manifest with cDC1 deficiency. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 802 CXCL9 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cDC1 are also important T cell chemoattractors to the tumor microenvironment through their production of CXCL9 and CXCL10, though it is unclear if cross-presentation is required in this setting. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 803 CXCL10 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cDC1 are also important T cell chemoattractors to the tumor microenvironment through their production of CXCL9 and CXCL10, though it is unclear if cross-presentation is required in this setting. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 804 IL12B 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cDC1 also provide cytokine support to T cells assisting in their effector functions. IL-12 is a well-known cDC1 produced factor that can drive CD8+ T cell cytolytic activity and secretion of IFN-γ Pan-cancer Inhibiting_recruitment_of_dendritic_cells 805 IL12A 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cDC1 also provide cytokine support to T cells assisting in their effector functions. IL-12 is a well-known cDC1 produced factor that can drive CD8+ T cell cytolytic activity and secretion of IFN-γ Pan-cancer Inhibiting_recruitment_of_dendritic_cells 806 IFNG 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cDC1 also provide cytokine support to T cells assisting in their effector functions. IL-12 is a well-known cDC1 produced factor that can drive CD8+ T cell cytolytic activity and secretion of IFN-γ Pan-cancer Inhibiting_recruitment_of_dendritic_cells 807 CD8A 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cDC1 also provide cytokine support to T cells assisting in their effector functions. IL-12 is a well-known cDC1 produced factor that can drive CD8+ T cell cytolytic activity and secretion of IFN-γ Pan-cancer Inhibiting_recruitment_of_dendritic_cells 808 CD8B 32332013 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells cDC1 also provide cytokine support to T cells assisting in their effector functions. IL-12 is a well-known cDC1 produced factor that can drive CD8+ T cell cytolytic activity and secretion of IFN-γ Pan-cancer Inhibiting_recruitment_of_dendritic_cells 809 IFNL3 38589249 Bladder cancer bladder cancer Inhibiting recruitment of dendritic cells In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Bladder_cancer Inhibiting_recruitment_of_dendritic_cells 810 FNDC3B 38581008 Pancreatic cancer pancreatic cancer Inhibiting recruitment of dendritic cells Additionally, ssGSEA analysis indicated a positive correlation between FNDC3B expression and infiltration of Th2 cells and neutrophils, while showing a negative correlation with plasmacytoid dendritic cells and Th17 cells infiltration. Pancreatic_cancer Inhibiting_recruitment_of_dendritic_cells 811 IL12B 38548896 Colon cancer colon adenocarcinoma, melanoma, triple negative breast cancer Inhibiting recruitment of dendritic cells Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 812 IL12B 38548896 Melanoma colon adenocarcinoma, melanoma, triple negative breast cancer Inhibiting recruitment of dendritic cells Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Melanoma Inhibiting_recruitment_of_dendritic_cells 813 IL12B 38548896 Breast cancer colon adenocarcinoma, melanoma, triple negative breast cancer Inhibiting recruitment of dendritic cells Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 814 IL12A 38548896 Colon cancer colon adenocarcinoma, melanoma, triple negative breast cancer Inhibiting recruitment of dendritic cells Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 815 IL12A 38548896 Melanoma colon adenocarcinoma, melanoma, triple negative breast cancer Inhibiting recruitment of dendritic cells Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Melanoma Inhibiting_recruitment_of_dendritic_cells 816 IL12A 38548896 Breast cancer colon adenocarcinoma, melanoma, triple negative breast cancer Inhibiting recruitment of dendritic cells Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 817 VEGFA 38528546 Lung cancer non-small cell lung cancer Inhibiting recruitment of dendritic cells Finally, the experimental validation results indicated that C. sinensis significantly decreased the VEGF and Ki67 expression, downregulated RhoA, Raf-1, and c-fos expression, which are related to cell migration and invasion, increased the serum concentration of hematopoietic factors (EPO and GM-CSF), and improved the percentage of immune cells (natural killer cells, dendritic cells, and CD4+ and CD8+ lymphocytes), which enhanced immune function. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 818 MKI67 38528546 Lung cancer non-small cell lung cancer Inhibiting recruitment of dendritic cells Finally, the experimental validation results indicated that C. sinensis significantly decreased the VEGF and Ki67 expression, downregulated RhoA, Raf-1, and c-fos expression, which are related to cell migration and invasion, increased the serum concentration of hematopoietic factors (EPO and GM-CSF), and improved the percentage of immune cells (natural killer cells, dendritic cells, and CD4+ and CD8+ lymphocytes), which enhanced immune function. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 819 RHOA 38528546 Lung cancer non-small cell lung cancer Inhibiting recruitment of dendritic cells Finally, the experimental validation results indicated that C. sinensis significantly decreased the VEGF and Ki67 expression, downregulated RhoA, Raf-1, and c-fos expression, which are related to cell migration and invasion, increased the serum concentration of hematopoietic factors (EPO and GM-CSF), and improved the percentage of immune cells (natural killer cells, dendritic cells, and CD4+ and CD8+ lymphocytes), which enhanced immune function. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 820 RAF1 38528546 Lung cancer non-small cell lung cancer Inhibiting recruitment of dendritic cells Finally, the experimental validation results indicated that C. sinensis significantly decreased the VEGF and Ki67 expression, downregulated RhoA, Raf-1, and c-fos expression, which are related to cell migration and invasion, increased the serum concentration of hematopoietic factors (EPO and GM-CSF), and improved the percentage of immune cells (natural killer cells, dendritic cells, and CD4+ and CD8+ lymphocytes), which enhanced immune function. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 821 FOS 38528546 Lung cancer non-small cell lung cancer Inhibiting recruitment of dendritic cells Finally, the experimental validation results indicated that C. sinensis significantly decreased the VEGF and Ki67 expression, downregulated RhoA, Raf-1, and c-fos expression, which are related to cell migration and invasion, increased the serum concentration of hematopoietic factors (EPO and GM-CSF), and improved the percentage of immune cells (natural killer cells, dendritic cells, and CD4+ and CD8+ lymphocytes), which enhanced immune function. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 822 PIK3C3 38506049 Colon cancer non-small-cell lung cancer, Renal cell carcinoma, melanoma, colon carcinoma, breast cancer Inhibiting recruitment of dendritic cells The combination of VPS34 inhibitor and STING agonist further induced cytokine release in both human and murine cancer cells as well as monocytic or dendritic innate immune cells. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 823 PIK3C3 38506049 Melanoma non-small-cell lung cancer, Renal cell carcinoma, melanoma, colon carcinoma, breast cancer Inhibiting recruitment of dendritic cells The combination of VPS34 inhibitor and STING agonist further induced cytokine release in both human and murine cancer cells as well as monocytic or dendritic innate immune cells. Melanoma Inhibiting_recruitment_of_dendritic_cells 824 PIK3C3 38506049 Breast cancer non-small-cell lung cancer, Renal cell carcinoma, melanoma, colon carcinoma, breast cancer Inhibiting recruitment of dendritic cells The combination of VPS34 inhibitor and STING agonist further induced cytokine release in both human and murine cancer cells as well as monocytic or dendritic innate immune cells. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 825 STING1 38506049 Colon cancer non-small-cell lung cancer, Renal cell carcinoma, melanoma, colon carcinoma, breast cancer Inhibiting recruitment of dendritic cells The combination of VPS34 inhibitor and STING agonist further induced cytokine release in both human and murine cancer cells as well as monocytic or dendritic innate immune cells. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 826 STING1 38506049 Melanoma non-small-cell lung cancer, Renal cell carcinoma, melanoma, colon carcinoma, breast cancer Inhibiting recruitment of dendritic cells The combination of VPS34 inhibitor and STING agonist further induced cytokine release in both human and murine cancer cells as well as monocytic or dendritic innate immune cells. Melanoma Inhibiting_recruitment_of_dendritic_cells 827 STING1 38506049 Breast cancer non-small-cell lung cancer, Renal cell carcinoma, melanoma, colon carcinoma, breast cancer Inhibiting recruitment of dendritic cells The combination of VPS34 inhibitor and STING agonist further induced cytokine release in both human and murine cancer cells as well as monocytic or dendritic innate immune cells. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 828 CGAS 38387885 Breast cancer breast cancer Inhibiting recruitment of dendritic cells The co-delivery of HfO2 /SN38 greatly enhances radiotherapy efficacy by effectively activating the cGAS-STING pathway, which then triggers dendritic cells maturation and CD8+ T cells recruitment. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 829 STING1 38387885 Breast cancer breast cancer Inhibiting recruitment of dendritic cells The co-delivery of HfO2 /SN38 greatly enhances radiotherapy efficacy by effectively activating the cGAS-STING pathway, which then triggers dendritic cells maturation and CD8+ T cells recruitment. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 830 RECQL4 38381090 Liver cancer hepatocellular carcinoma Inhibiting recruitment of dendritic cells Mechanistically, the inhibitory effect of RECQL4 on radiotherapy is due to the reduced recruitment of dendritic cells and CD8+ T cells in the tumor microenvironment (TME). Liver_cancer Inhibiting_recruitment_of_dendritic_cells 831 XCL1 38346928 Melanoma melanoma Inhibiting recruitment of dendritic cells Intratumoral delivery of a highly active form of XCL1 enhances antitumor CTL responses through recruitment of CXCL9-expressing conventional type-1 dendritic cells. Melanoma Inhibiting_recruitment_of_dendritic_cells 832 CXCL9 38346928 Melanoma melanoma Inhibiting recruitment of dendritic cells Intratumoral delivery of a highly active form of XCL1 enhances antitumor CTL responses through recruitment of CXCL9-expressing conventional type-1 dendritic cells. Melanoma Inhibiting_recruitment_of_dendritic_cells 833 CGAS 38336268 Breast cancer breast cancer Inhibiting recruitment of dendritic cells The released Mn2+ not only catalysed a Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also activated the cGAS-STING pathway to boost dendritic cell (DC) maturation. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 834 STING1 38336268 Breast cancer breast cancer Inhibiting recruitment of dendritic cells The released Mn2+ not only catalysed a Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also activated the cGAS-STING pathway to boost dendritic cell (DC) maturation. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 835 IFNG 38281989 Gastrointestinal cancer gastric cancer Inhibiting recruitment of dendritic cells Activation of iNKT cells by tumor lipid antigens can trigger direct cytotoxicity and promote indirect anti-tumor immune responses such as recruitment and activation of T cells, NK cells, and dendritic cells through secretion of cytokines and IFNγ. Gastrointestinal_cancer Inhibiting_recruitment_of_dendritic_cells 836 CTNNB1 38280119 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells Overactive β-catenin signaling hampers dendritic cell (DC) recruitment, promotes CD8+ T cell exclusion and increases the population of regulatory T cells (Tregs). Pan-cancer Inhibiting_recruitment_of_dendritic_cells 837 TNF 38195677 Colon cancer colorectal cancer Inhibiting recruitment of dendritic cells TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 838 PANX1 38195677 Colon cancer colorectal cancer Inhibiting recruitment of dendritic cells TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 839 CASP8 38195677 Colon cancer colorectal cancer Inhibiting recruitment of dendritic cells TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 840 CASP3 38195677 Colon cancer colorectal cancer Inhibiting recruitment of dendritic cells TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 841 ASCC3 38148115 Lung cancer non-small cell lung cancer Inhibiting recruitment of dendritic cells Overexpression of ASCC3 promoted malignant phenotypes of NSCLC cells and induced an immunosuppressive tumor microenvironment, which was characterized by a decrease in CD8+ T cells, natural killer cells and dendritic cells but an increase in regulatory T(Treg) cells. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 842 PEF1 38042523 Breast cancer breast Cancer Inhibiting recruitment of dendritic cells PEF increased innate immune activation, with enhanced recruitment of dendritic cells, M1 macrophages, and natural killer cells coupled with a reduction in M2 macrophages and myeloid-derived suppressor cells (all P < .05). Breast_cancer Inhibiting_recruitment_of_dendritic_cells 843 CCDC69 37828454 Breast cancer breast cancer Inhibiting recruitment of dendritic cells The expression of CCDC69 was found to be positively correlated with multiple tumor-suppression immune infiltration cells, especially T cells and dendritic cells. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 844 IL7 37790917 Melanoma melanoma Inhibiting recruitment of dendritic cells Herein, we engineered attenuated Salmonella typhimurium VNP20009 with gene circuits to synthetize granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 7 (IL-7) within tumors, which recruited dendritic cells (DCs) and enhanced T cell priming to elicit anti-tumor response. Melanoma Inhibiting_recruitment_of_dendritic_cells 845 CCL21 37730274 Lung cancer non-small cell lung cancer Inhibiting recruitment of dendritic cells In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 846 UBA3 37656220 Lung cancer lung adenocarcinoma Inhibiting recruitment of dendritic cells Moreover, the overexpression of UBA3 in LUAD cells was associated with the secretion of these cytokines, and the recruitment and infiltration of immunosuppressive cells including tumor-associated macrophages (TAMs), plasmacytoid dendritic cells (pDCs), Th2 cells and T-regulatory cells (Tregs). Lung_cancer Inhibiting_recruitment_of_dendritic_cells 847 TAM 37532692 Lung cancer lung adenocarcinoma Inhibiting recruitment of dendritic cells The enrichment of TAM-FOLR2 in IA might result from alveolar resident macrophage-resistin (ARM-RETN) transformation and recruitment of dendritic cells (DCs) and other TAMs, as evidenced by temporal trajectories and differential expression profiles of chemokine ligands/receptors versus those in the early stages of tumors. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 848 FOLR2 37532692 Lung cancer lung adenocarcinoma Inhibiting recruitment of dendritic cells The enrichment of TAM-FOLR2 in IA might result from alveolar resident macrophage-resistin (ARM-RETN) transformation and recruitment of dendritic cells (DCs) and other TAMs, as evidenced by temporal trajectories and differential expression profiles of chemokine ligands/receptors versus those in the early stages of tumors. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 849 FLT3LG 37487664 Lymphoma lymphoma Inhibiting recruitment of dendritic cells We recently described an ISV using Flt3L to expand and recruit dendritic cells (DC), radiotherapy to load DC with TA, and pattern recognition receptor agonists (PRRa) to activate TA-loaded DC. Lymphoma Inhibiting_recruitment_of_dendritic_cells 850 CARD9 37089447 Pancreatic cancer pancreatic cancer Inhibiting recruitment of dendritic cells CARD9 deficiency promotes pancreatic cancer growth by blocking dendritic cell maturation via SLC6A8-mediated creatine transport. Pancreatic_cancer Inhibiting_recruitment_of_dendritic_cells 851 SLC6A8 37089447 Pancreatic cancer pancreatic cancer Inhibiting recruitment of dendritic cells CARD9 deficiency promotes pancreatic cancer growth by blocking dendritic cell maturation via SLC6A8-mediated creatine transport. Pancreatic_cancer Inhibiting_recruitment_of_dendritic_cells 852 CCL5 37079538 Bone cancer osteosarcoma Inhibiting recruitment of dendritic cells Resultant expression of soluble mediators such as CCL5 and CXCL10 can facilitate recruitment of dendritic cells and immune effector cells into the tumor. Bone_cancer Inhibiting_recruitment_of_dendritic_cells 853 CXCL10 37079538 Bone cancer osteosarcoma Inhibiting recruitment of dendritic cells Resultant expression of soluble mediators such as CCL5 and CXCL10 can facilitate recruitment of dendritic cells and immune effector cells into the tumor. Bone_cancer Inhibiting_recruitment_of_dendritic_cells 854 IL1B 37040466 Breast cancer breast cancer, colon cancer, lung cancer Inhibiting recruitment of dendritic cells Accompanying these effects, blockade of IL1β alone or in combination induced significant remodeling of the tumor microenvironment (TME), with decreased numbers of immune suppressive cells and increased tumor infiltration by dendritic cells (DC) and effector T cells. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 855 IL1B 37040466 Colon cancer breast cancer, colon cancer, lung cancer Inhibiting recruitment of dendritic cells Accompanying these effects, blockade of IL1β alone or in combination induced significant remodeling of the tumor microenvironment (TME), with decreased numbers of immune suppressive cells and increased tumor infiltration by dendritic cells (DC) and effector T cells. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 856 IL1B 37040466 Lung cancer breast cancer, colon cancer, lung cancer Inhibiting recruitment of dendritic cells Accompanying these effects, blockade of IL1β alone or in combination induced significant remodeling of the tumor microenvironment (TME), with decreased numbers of immune suppressive cells and increased tumor infiltration by dendritic cells (DC) and effector T cells. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 857 CCL20 36888717 Colon cancer colorectal and breast cancer Inhibiting recruitment of dendritic cells Furthermore, we target the presentation of tumor-derived antigens by dendritic cells, using a second engineered bacterial strain expressing CCL20. This led to type 1 conventional dendritic cell recruitment and synergized with hCXCL16K42A-induced T cell recruitment to provide additional therapeutic benefit. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 858 CCL20 36888717 Breast cancer colorectal and breast cancer Inhibiting recruitment of dendritic cells Furthermore, we target the presentation of tumor-derived antigens by dendritic cells, using a second engineered bacterial strain expressing CCL20. This led to type 1 conventional dendritic cell recruitment and synergized with hCXCL16K42A-induced T cell recruitment to provide additional therapeutic benefit. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 859 CDCA8 36855818 Liver cancer hepatocellular carcinoma Inhibiting recruitment of dendritic cells We observed a direct link between CDCA8 levels and Th2 and T helper cells, and a negative link between CDCA8 levels and dendritic cells (DC), neutrophils, cytotoxic cells, and CD8 T cells. Liver_cancer Inhibiting_recruitment_of_dendritic_cells 860 PGK1 36358653 Lung cancer Lung Adenocarcinoma Inhibiting recruitment of dendritic cells Furthermore, PGK1 is also linked to the recruitment of numerous immune cells, including aDC (dendritic cells), macrophages, and neutrophils. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 861 IL33 36256464 Pancreatic cancer pancreatic ductal adenocarcinoma Inhibiting recruitment of dendritic cells Our data indicate that this shift in antitumor immunity is influenced by increased levels of IL-33, which increases dendritic cell and cytotoxic T cell activity. Pancreatic_cancer Inhibiting_recruitment_of_dendritic_cells 862 TPPP3 36058091 Head and neck cancer head and neck squamous cell carcinoma Inhibiting recruitment of dendritic cells TPPP3 expression was significantly positively correlated with infiltration level of B cell plasma and myeloid dendritic cells activated in HNSC, while it was negatively correlated with infiltration level of Tregs cells, CD8+ T cells, B cell memory. Head_and_neck_cancer Inhibiting_recruitment_of_dendritic_cells 863 SMAD4 35863523 Colon cancer colon carcinoma Inhibiting recruitment of dendritic cells SMAD4 loss in mouse colon epithelium led to enlarged gut-associated lymphoid tissues and recruitment of immune cells to the mouse colon epithelium and stroma, particularly T regulatory, Th17, and dendritic cells. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 864 CD47 35367532 Liver cancer hepatocellular carcinoma Inhibiting recruitment of dendritic cells Blockade of the cell surface protein CD47 resulted in activation of CD103+ dendritic cells which led to the recruitment and activation of natural killer cells (a different immune cell). Liver_cancer Inhibiting_recruitment_of_dendritic_cells 865 ITGAE 35367532 Liver cancer hepatocellular carcinoma Inhibiting recruitment of dendritic cells Blockade of the cell surface protein CD47 resulted in activation of CD103+ dendritic cells which led to the recruitment and activation of natural killer cells (a different immune cell). Liver_cancer Inhibiting_recruitment_of_dendritic_cells 866 TLR3 35250293 Other cancers esophageal squamous cell carcinoma Inhibiting recruitment of dendritic cells Overexpression of TLR3 resulted in an immune-active microenvironment via the recruitment of immune-active cells including cytotoxic lymphocytes (CTLs), CD8+ T cells, NK cells, dendritic cells, and M1-type macrophages. Other_cancers Inhibiting_recruitment_of_dendritic_cells 867 YTHDF1 35193930 Gastrointestinal cancer Gastric cancer Inhibiting recruitment of dendritic cells Loss of YTHDF1 in gastric tumors restores sensitivity to antitumor immunity by recruiting mature dendritic cells. Gastrointestinal_cancer Inhibiting_recruitment_of_dendritic_cells 868 DIAPH3 35056735 Renal cancer clear renal cell carcinoma Inhibiting recruitment of dendritic cells Meanwhile, DRF3 showed excellent biocompatibility, could sustainably and slowly release antigens, recruit dendritic cells and promote the maturation of dendritic cells (DCs) in vitro. Renal_cancer Inhibiting_recruitment_of_dendritic_cells 869 STAT3 35047999 Head and neck cancer head and neck squamous cell carcinoma Inhibiting recruitment of dendritic cells First, STAT3 is often overactivated in HNSCC and induces the secretion of immunosuppressive cytokines, thereby promoting recruitment of immune suppressive regulatory T cells and myeloid-derived suppressor cells to the tumor microenvironment (TME) while hampering the development of dendritic cells. Head_and_neck_cancer Inhibiting_recruitment_of_dendritic_cells 870 IL12B 34855754 Melanoma melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Melanoma Inhibiting_recruitment_of_dendritic_cells 871 IL12B 34855754 Brain cancer melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Brain_cancer Inhibiting_recruitment_of_dendritic_cells 872 IL12B 34855754 Colon cancer melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 873 IL12B 34855754 Lymphoma melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Lymphoma Inhibiting_recruitment_of_dendritic_cells 874 IL12B 34855754 Other cancers melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Other_cancers Inhibiting_recruitment_of_dendritic_cells 875 IL12B 34855754 Breast cancer melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 876 IL12A 34855754 Melanoma melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Melanoma Inhibiting_recruitment_of_dendritic_cells 877 IL12A 34855754 Brain cancer melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Brain_cancer Inhibiting_recruitment_of_dendritic_cells 878 IL12A 34855754 Colon cancer melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 879 IL12A 34855754 Lymphoma melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Lymphoma Inhibiting_recruitment_of_dendritic_cells 880 IL12A 34855754 Other cancers melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Other_cancers Inhibiting_recruitment_of_dendritic_cells 881 IL12A 34855754 Breast cancer melanoma, glioma, colon carcinoma, lymphoma, mastocytoma, breast cancer Inhibiting recruitment of dendritic cells Intratumoral administration of either IL12 vector platform resulted in recruitment of immune cells, including effector T cells and dendritic cells, and the complete remission of established tumors in multiple murine models. Breast_cancer Inhibiting_recruitment_of_dendritic_cells 882 ADAM12 34604068 Colon cancer Colon Adenocarcinoma Inhibiting recruitment of dendritic cells Moreover, ADAM12 expression significantly correlated with the abundance of CD4+ T cells, B cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, and their markers, as well as lymphocytes, immunomodulators, and chemokines. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 883 CCL21 34402138 Pancreatic cancer pancreatic cancer Inhibiting recruitment of dendritic cells Chemokine C-C motif ligand 21 (CCL21), a chemokine promoting T cell immunity by recruiting and colocalizing dendritic cells (DCs) and T cells, serves as a potential antitumor agent in many cancers. Pancreatic_cancer Inhibiting_recruitment_of_dendritic_cells 884 CCL3 34277113 Colon cancer colon carcinoma, lung carcinoma, cervical cancer, melanoma, lymphoma Inhibiting recruitment of dendritic cells Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 885 CCL3 34277113 Lung cancer colon carcinoma, lung carcinoma, cervical cancer, melanoma, lymphoma Inhibiting recruitment of dendritic cells Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Lung_cancer Inhibiting_recruitment_of_dendritic_cells 886 CCL3 34277113 Other cancers colon carcinoma, lung carcinoma, cervical cancer, melanoma, lymphoma Inhibiting recruitment of dendritic cells Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Other_cancers Inhibiting_recruitment_of_dendritic_cells 887 CCL3 34277113 Melanoma colon carcinoma, lung carcinoma, cervical cancer, melanoma, lymphoma Inhibiting recruitment of dendritic cells Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Melanoma Inhibiting_recruitment_of_dendritic_cells 888 CCL3 34277113 Lymphoma colon carcinoma, lung carcinoma, cervical cancer, melanoma, lymphoma Inhibiting recruitment of dendritic cells Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Lymphoma Inhibiting_recruitment_of_dendritic_cells 889 AHR 34223158 Pan-cancer review, pan-cancer Inhibiting recruitment of dendritic cells AHR activation also stimulates the formation and recruitment of tolerogenic dendritic cells, tumor associated macrophages, and regulatory T cells in the tumor microenvironment, which restrains antitumoral immune response. Pan-cancer Inhibiting_recruitment_of_dendritic_cells 890 STING1 34182334 Colon cancer colorectal cancer Inhibiting recruitment of dendritic cells Our findings demonstrated that STING agonist diABZI combined with IDO inhibitor 1-MT significantly inhibited tumor growth, even better than the three-drug combination, promoted the recruitment of CD8+ T cells and dendritic cells, and decreased the infiltration of myeloid-derived suppressor cells. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 891 IDO1 34182334 Colon cancer colorectal cancer Inhibiting recruitment of dendritic cells Our findings demonstrated that STING agonist diABZI combined with IDO inhibitor 1-MT significantly inhibited tumor growth, even better than the three-drug combination, promoted the recruitment of CD8+ T cells and dendritic cells, and decreased the infiltration of myeloid-derived suppressor cells. Colon_cancer Inhibiting_recruitment_of_dendritic_cells 892 CTNNB1 33574942 Melanoma melanoma Inhibiting recruitment of dendritic cells β-catenin expression by tumor cells suppressed dendritic cell recruitment to the tumor microenvironment in a melanoma model, resulting in fewer tumor-infiltrating lymphocytes. Melanoma Inhibiting_recruitment_of_dendritic_cells 893 SELPLG 27192578 Melanoma melanoma T cell dysfunction and exhaustion In models of melanoma cancer in which T cell dysfunction occurs, PSGL-1 deficiency led to PD-1 downregulation, improved T cell responses, and tumor control. Thus, PSGL-1 plays a fundamental role in balancing viral control and immunopathology and also functions to regulate T cell responses in the tumor microenvironment. Melanoma T_cell_dysfunction_and_exhaustion 894 YAP1 38652549 Other cancers sarcoma T cell dysfunction and exhaustion YAP1 promotes collagen VI (COLVI) deposition in the UPS TME. In turn, COLVI induces CD8+ T cell dysfunction and immune evasion by remodeling fibrillar collagen and inhibiting T cell autophagic flux. Other_cancers T_cell_dysfunction_and_exhaustion 895 LAG3 38589688 liver cancer liver cancer T cell dysfunction and exhaustion Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. liver_cancer T_cell_dysfunction_and_exhaustion 896 TGFB1 38574299 Myeloma myeloma T cell dysfunction and exhaustion Finally, we demonstrate that non-classical monocytes are enriched in the myeloma niche and may induce CAR-T cell dysfunction through mechanisms that include TGFβ. Myeloma T_cell_dysfunction_and_exhaustion 897 LGALS1 38545824 Renal cancer renal cell carcinoma T cell dysfunction and exhaustion High galectin-1 indicated therapeutic resistance and shorter PFS of IO/TKI therapy. High galectin-1 also indicated CD8+ T cell dysfunction. Renal_cancer T_cell_dysfunction_and_exhaustion 898 LAG3 38486998 Renal cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Renal_cancer T_cell_dysfunction_and_exhaustion 899 LAG3 38486998 Leukemia renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Leukemia T_cell_dysfunction_and_exhaustion 900 LAG3 38486998 Melanoma renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Melanoma T_cell_dysfunction_and_exhaustion 901 LAG3 38486998 Lung cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Lung_cancer T_cell_dysfunction_and_exhaustion 902 LAG3 38486998 liver cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). liver_cancer T_cell_dysfunction_and_exhaustion 903 LAG3 38486998 Head and neck cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Head_and_neck_cancer T_cell_dysfunction_and_exhaustion 904 LAG3 38486998 Prostate cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Prostate_cancer T_cell_dysfunction_and_exhaustion 905 LAG3 38486998 Lung cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Lung_cancer T_cell_dysfunction_and_exhaustion 906 FGL1 38486998 Renal cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Renal_cancer T_cell_dysfunction_and_exhaustion 907 FGL1 38486998 Leukemia renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Leukemia T_cell_dysfunction_and_exhaustion 908 FGL1 38486998 Melanoma renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Melanoma T_cell_dysfunction_and_exhaustion 909 FGL1 38486998 Lung cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Lung_cancer T_cell_dysfunction_and_exhaustion 910 FGL1 38486998 liver cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). liver_cancer T_cell_dysfunction_and_exhaustion 911 FGL1 38486998 Head and neck cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Head_and_neck_cancer T_cell_dysfunction_and_exhaustion 912 FGL1 38486998 Prostate cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Prostate_cancer T_cell_dysfunction_and_exhaustion 913 FGL1 38486998 Lung cancer renal cell carcinoma, leukemia, melanoma, lung squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma , lung adenocarcinoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Lung_cancer T_cell_dysfunction_and_exhaustion 914 FFAR2 38402237 Lung cancer lung adenocarcinoma T cell dysfunction and exhaustion FFAR2 inhibition overcame resistance to immune checkpoint blockade through enhancing the recruitment and cytotoxicity of tumor-infiltrating T cells. Lung_cancer T_cell_dysfunction_and_exhaustion 915 STAT3 38278025 Colon cancer colorectal cancer T cell dysfunction and exhaustion Network pharmacology and clinical databases suggested that the STAT3/ Galectin-3(Gal-3)/LAG3 pathway might be APS's potential target for treating CRC and associated with CD8+ T cell dysfunction. Colon_cancer T_cell_dysfunction_and_exhaustion 916 LGALS3 38278025 Colon cancer colorectal cancer T cell dysfunction and exhaustion Network pharmacology and clinical databases suggested that the STAT3/ Galectin-3(Gal-3)/LAG3 pathway might be APS's potential target for treating CRC and associated with CD8+ T cell dysfunction. Colon_cancer T_cell_dysfunction_and_exhaustion 917 LAG3 38278025 Colon cancer colorectal cancer T cell dysfunction and exhaustion Network pharmacology and clinical databases suggested that the STAT3/ Galectin-3(Gal-3)/LAG3 pathway might be APS's potential target for treating CRC and associated with CD8+ T cell dysfunction. Colon_cancer T_cell_dysfunction_and_exhaustion 918 MAP4K1 38101218 Lung cancer Non-Small Cell Lung Cancer T cell dysfunction and exhaustion Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Lung_cancer T_cell_dysfunction_and_exhaustion 919 ACLY 38055816 liver cancer liver cancer, melanoma, pancreatic cancer T cell dysfunction and exhaustion Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. liver_cancer T_cell_dysfunction_and_exhaustion 920 ACLY 38055816 Melanoma liver cancer, melanoma, pancreatic cancer T cell dysfunction and exhaustion Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. Melanoma T_cell_dysfunction_and_exhaustion 921 ACLY 38055816 Pancreatic cancer liver cancer, melanoma, pancreatic cancer T cell dysfunction and exhaustion Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. Pancreatic_cancer T_cell_dysfunction_and_exhaustion 922 CD274 38055816 liver cancer liver cancer, melanoma, pancreatic cancer T cell dysfunction and exhaustion Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. liver_cancer T_cell_dysfunction_and_exhaustion 923 CD274 38055816 Melanoma liver cancer, melanoma, pancreatic cancer T cell dysfunction and exhaustion Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. Melanoma T_cell_dysfunction_and_exhaustion 924 CD274 38055816 Pancreatic cancer liver cancer, melanoma, pancreatic cancer T cell dysfunction and exhaustion Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. Pancreatic_cancer T_cell_dysfunction_and_exhaustion 925 BMI1 37562671 Liver cancer hepatocellular carcinoma T cell dysfunction and exhaustion Moreover, liver-specific BMI1 knockdown proves beneficial in ameliorating T cell dysfunction and decelerating HCC progression. Liver_cancer T_cell_dysfunction_and_exhaustion 926 MRGPRX3 37308665 Oral cancer oral cavity squamous cell carcinoma, colon adenocarcinoma T cell dysfunction and exhaustion The GPCR-Gα(s)-PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure. Oral_cancer T_cell_dysfunction_and_exhaustion 927 MRGPRX3 37308665 Colon cancer oral cavity squamous cell carcinoma, colon adenocarcinoma T cell dysfunction and exhaustion The GPCR-Gα(s)-PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure. Colon_cancer T_cell_dysfunction_and_exhaustion 928 GNAS 37308665 Oral cancer oral cavity squamous cell carcinoma, colon adenocarcinoma T cell dysfunction and exhaustion The GPCR-Gα(s)-PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure. Oral_cancer T_cell_dysfunction_and_exhaustion 929 GNAS 37308665 Colon cancer oral cavity squamous cell carcinoma, colon adenocarcinoma T cell dysfunction and exhaustion The GPCR-Gα(s)-PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure. Colon_cancer T_cell_dysfunction_and_exhaustion 930 PRKACA 37308665 Oral cancer oral cavity squamous cell carcinoma, colon adenocarcinoma T cell dysfunction and exhaustion The GPCR-Gα(s)-PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure. Oral_cancer T_cell_dysfunction_and_exhaustion 931 PRKACA 37308665 Colon cancer oral cavity squamous cell carcinoma, colon adenocarcinoma T cell dysfunction and exhaustion The GPCR-Gα(s)-PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure. Colon_cancer T_cell_dysfunction_and_exhaustion 932 CTLA4 37268394 Pancreatic cancer pancreatic ductal adenocarcinoma T cell dysfunction and exhaustion The immune checkpoint proteins (ICPs), including CTLA-4, PD-1, PD-L1, and PD-L2, are critical players in T cell dysfunction and pancreatic tumor cell growth. Pancreatic_cancer T_cell_dysfunction_and_exhaustion 933 PDCD1 37268394 Pancreatic cancer pancreatic ductal adenocarcinoma T cell dysfunction and exhaustion The immune checkpoint proteins (ICPs), including CTLA-4, PD-1, PD-L1, and PD-L2, are critical players in T cell dysfunction and pancreatic tumor cell growth. Pancreatic_cancer T_cell_dysfunction_and_exhaustion 934 CD274 37268394 Pancreatic cancer pancreatic ductal adenocarcinoma T cell dysfunction and exhaustion The immune checkpoint proteins (ICPs), including CTLA-4, PD-1, PD-L1, and PD-L2, are critical players in T cell dysfunction and pancreatic tumor cell growth. Pancreatic_cancer T_cell_dysfunction_and_exhaustion 935 PDCD1LG2 37268394 Pancreatic cancer pancreatic ductal adenocarcinoma T cell dysfunction and exhaustion The immune checkpoint proteins (ICPs), including CTLA-4, PD-1, PD-L1, and PD-L2, are critical players in T cell dysfunction and pancreatic tumor cell growth. Pancreatic_cancer T_cell_dysfunction_and_exhaustion 936 HAVCR2 37148978 Colon cancer colorectal cancer, prostate cancer T cell dysfunction and exhaustion T cell immunoglobulin and mucin domain 3 (TIM-3), a non-redundant immune checkpoint, synergizes with PD-1 to mediate T cell dysfunction in tumor microenvironment. Colon_cancer T_cell_dysfunction_and_exhaustion 937 HAVCR2 37148978 Prostate cancer colorectal cancer, prostate cancer T cell dysfunction and exhaustion T cell immunoglobulin and mucin domain 3 (TIM-3), a non-redundant immune checkpoint, synergizes with PD-1 to mediate T cell dysfunction in tumor microenvironment. Prostate_cancer T_cell_dysfunction_and_exhaustion 938 PDCD1 37148978 Colon cancer colorectal cancer, prostate cancer T cell dysfunction and exhaustion T cell immunoglobulin and mucin domain 3 (TIM-3), a non-redundant immune checkpoint, synergizes with PD-1 to mediate T cell dysfunction in tumor microenvironment. Colon_cancer T_cell_dysfunction_and_exhaustion 939 PDCD1 37148978 Prostate cancer colorectal cancer, prostate cancer T cell dysfunction and exhaustion T cell immunoglobulin and mucin domain 3 (TIM-3), a non-redundant immune checkpoint, synergizes with PD-1 to mediate T cell dysfunction in tumor microenvironment. Prostate_cancer T_cell_dysfunction_and_exhaustion 940 PPARG 37019619 Liver cancer hepatocellular carcinoma T cell dysfunction and exhaustion Mechanistically, tumour cell-intrinsic upregulation of peroxisome proliferator-activated receptor-gamma (PPARγ) transcriptionally activated vascular endothelial growth factor-A (VEGF-A) production to drive MDSC expansion and CD8+ T cell dysfunction. Liver_cancer T_cell_dysfunction_and_exhaustion 941 VEGFA 37019619 Liver cancer hepatocellular carcinoma T cell dysfunction and exhaustion Mechanistically, tumour cell-intrinsic upregulation of peroxisome proliferator-activated receptor-gamma (PPARγ) transcriptionally activated vascular endothelial growth factor-A (VEGF-A) production to drive MDSC expansion and CD8+ T cell dysfunction. Liver_cancer T_cell_dysfunction_and_exhaustion 942 CD274 36733484 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion Modulation of TME is useful for improving therapy strategies. PD-L1 protein on tumor cells interacts with PD-1 protein on T cells, contributing to T cell dysfunction and exhaustion, blockage of the immune response. Pan-cancer T_cell_dysfunction_and_exhaustion 943 PDCD1 36733484 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion Modulation of TME is useful for improving therapy strategies. PD-L1 protein on tumor cells interacts with PD-1 protein on T cells, contributing to T cell dysfunction and exhaustion, blockage of the immune response. Pan-cancer T_cell_dysfunction_and_exhaustion 944 PDCD1 36698265 Brain cancer glioblastoma T cell dysfunction and exhaustion They ameliorate the T cell dysfunction through the double roles of loaded JQ1, which simultaneously decreases the expression of PD-1 and TIM-3 on T cells, and the expression of PD-L1 on tumor cells. Brain_cancer T_cell_dysfunction_and_exhaustion 945 CD274 36698265 Brain cancer glioblastoma T cell dysfunction and exhaustion They ameliorate the T cell dysfunction through the double roles of loaded JQ1, which simultaneously decreases the expression of PD-1 and TIM-3 on T cells, and the expression of PD-L1 on tumor cells. Brain_cancer T_cell_dysfunction_and_exhaustion 946 HAVCR2 36698265 Brain cancer glioblastoma T cell dysfunction and exhaustion They ameliorate the T cell dysfunction through the double roles of loaded JQ1, which simultaneously decreases the expression of PD-1 and TIM-3 on T cells, and the expression of PD-L1 on tumor cells. Brain_cancer T_cell_dysfunction_and_exhaustion 947 PRDM1 36350986 Leukemia leukemia T cell dysfunction and exhaustion However, in the setting of PRDM1 deficiency, a negative epigenetic feedback program of nuclear factor of activated T cells (NFAT)-driven T cell dysfunction was identified. Leukemia T_cell_dysfunction_and_exhaustion 948 PSAT1 36105075 Breast cancer Breast Cancer T cell dysfunction and exhaustion In addition, PSAT1 hypermethylation is associated with T cell dysfunction and shortened survival time in BRCA. Breast_cancer T_cell_dysfunction_and_exhaustion 949 CD8A 36035168 Pan-cancer pan-cancer T cell dysfunction and exhaustion Besides, epigenetic modifications of CD8A were related to CTL levels and T cell dysfunctional states, thereby affecting survival outcomes of specific cancer types. Pan-cancer T_cell_dysfunction_and_exhaustion 950 TDO2 35972800 Oral cancer oral cancer T cell dysfunction and exhaustion Functional experiments revealed that TDO2+ myofibroblasts were more likely to possess the ability for chemotaxis toward T cells but induced the transformation of CD4+ T cells into Tregs and caused CD8+ T cell dysfunction. Oral_cancer T_cell_dysfunction_and_exhaustion 951 HIF1A 35840558 Breast cancer triple-negative breast cancer T cell dysfunction and exhaustion We demonstrate that hypoxia-induced factor 1α (HIF1α) interaction with HDAC1 and concurrent PRC2 dependency causes chromatin remolding resulting in epigenetic suppression of effector genes and subsequent immune dysfunction. Breast_cancer T_cell_dysfunction_and_exhaustion 952 HDAC1 35840558 Breast cancer triple-negative breast cancer T cell dysfunction and exhaustion We demonstrate that hypoxia-induced factor 1α (HIF1α) interaction with HDAC1 and concurrent PRC2 dependency causes chromatin remolding resulting in epigenetic suppression of effector genes and subsequent immune dysfunction. Breast_cancer T_cell_dysfunction_and_exhaustion 953 TIGIT 35554512 Lymphoma Lymphoma T cell dysfunction and exhaustion Utilizing in vitro and in vivo studies, we demonstrate that TIGIT blockade alone improves the antitumor function of CAR-T cells. Altogether, we provide evidence of CAR-T cell dysfunction marked by TIGIT expression driving a poor response in patients with NHL. Lymphoma T_cell_dysfunction_and_exhaustion 954 IRF4 35544467 Leukemia chronic myeloid leukemia T cell dysfunction and exhaustion We for the first time observed the altered gene expression profiles of CD3+ T cells from CML patients, and the results suggested that IRF4, BACH2 and NFATC1 may be involved in regulating T cell dysfunction in CML patients in the form of a transcriptional regulatory network. Leukemia T_cell_dysfunction_and_exhaustion 955 BACH2 35544467 Leukemia chronic myeloid leukemia T cell dysfunction and exhaustion We for the first time observed the altered gene expression profiles of CD3+ T cells from CML patients, and the results suggested that IRF4, BACH2 and NFATC1 may be involved in regulating T cell dysfunction in CML patients in the form of a transcriptional regulatory network. Leukemia T_cell_dysfunction_and_exhaustion 956 NFATC1 35544467 Leukemia chronic myeloid leukemia T cell dysfunction and exhaustion We for the first time observed the altered gene expression profiles of CD3+ T cells from CML patients, and the results suggested that IRF4, BACH2 and NFATC1 may be involved in regulating T cell dysfunction in CML patients in the form of a transcriptional regulatory network. Leukemia T_cell_dysfunction_and_exhaustion 957 AR 35420889 Bladder cancer bladder cancer T cell dysfunction and exhaustion The T cell-intrinsic function of AR in promoting CD8+ T cell exhaustion in vivo was established using multiple approaches including loss-of-function studies with CD8-specific Ar knockout mice. Bladder_cancer T_cell_dysfunction_and_exhaustion 958 TREM2 35278107 Lung cancer non-small cell lung cancer T cell dysfunction and exhaustion TREM2+ TAMs were enriched with multiple anti-inflammatory cytokines, exhibiting a M2-like immunosuppressive phenotype, and potentiate T cell dysfunction including impaired anti-tumor activity of CD8+ T cells and enhanced differentiation towards FOXP3+ Tregs, thus facilitating immune evasion of NSCLC. Lung_cancer T_cell_dysfunction_and_exhaustion 959 IRAK4 35271824 Pancreatic cancer pancreatic ductal adenocarcinoma T cell dysfunction and exhaustion Loss of IRAK4 abrogates NF-κB activity, several immunosuppressive factors, checkpoint ligands, and hyaluronan synthase 2, all of which drive T cell dysfunction. Pancreatic_cancer T_cell_dysfunction_and_exhaustion 960 NFKB1 35271824 Pancreatic cancer pancreatic ductal adenocarcinoma T cell dysfunction and exhaustion Loss of IRAK4 abrogates NF-κB activity, several immunosuppressive factors, checkpoint ligands, and hyaluronan synthase 2, all of which drive T cell dysfunction. Pancreatic_cancer T_cell_dysfunction_and_exhaustion 961 HAS2 35271824 Pancreatic cancer pancreatic ductal adenocarcinoma T cell dysfunction and exhaustion Loss of IRAK4 abrogates NF-κB activity, several immunosuppressive factors, checkpoint ligands, and hyaluronan synthase 2, all of which drive T cell dysfunction. Pancreatic_cancer T_cell_dysfunction_and_exhaustion 962 KISS1R 35224894 Lung cancer Lung Cancer T cell dysfunction and exhaustion Accordingly, administration of kisspeptin-10 significantly impairs T cell function, whereas knockout of Gpr54 in T cells inhibits lung tumor progression by suppressing T cell dysfunction and exhaustion with or without AR. Lung_cancer T_cell_dysfunction_and_exhaustion 963 ESR1 34907918 Melanoma melanoma T cell dysfunction and exhaustion Using transcriptomics and preclinical melanoma models, the authors show that ERα signaling in tumor-associated macrophages contributed to an immune-suppressive state within the tumor microenvironment (TME) by promoting CD8+ T cell dysfunction and exhaustion. Melanoma T_cell_dysfunction_and_exhaustion 964 KLRB1 34881489 Brain cancer glioma T cell dysfunction and exhaustion The expression of CD161 was closely related to the pathology and molecular pathology of glioma. Meanwhile, CD161 promoted the progression and evolution of gliomas through its unique effect on T cell dysfunction. Brain_cancer T_cell_dysfunction_and_exhaustion 965 TOX 34873490 Leukemia acute myeloid leukemia T cell dysfunction and exhaustion Moreover, the TOX gene was found to be correlated with lactate production and implicated in CD8+ T cell dysfunction. Leukemia T_cell_dysfunction_and_exhaustion 966 USP7 34753486 Lung cancer non-small cell lung cancer T cell dysfunction and exhaustion Increased levels of circUSP7 indicate poor clinical prognosis and CD8+ T cell dysfunction in patients with NSCLC. Lung_cancer T_cell_dysfunction_and_exhaustion 967 HAVCR2 34725458 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion TIM3 indicated CD8+ T cell dysfunction, which impeded chemotherapeutic responsiveness. Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 968 TIGIT 34659197 Colon cancer colorectal cancer T cell dysfunction and exhaustion These results suggest that while TIGIT induces CD3+ T cell dysfunction in colorectal cancer, co-targeting TIGIT and PD-1 can lead to an effective antitumor response and may serve as a novel therapeutic strategy for colorectal patients. Colon_cancer T_cell_dysfunction_and_exhaustion 969 NT5E 34508993 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion High CD73 expression indicated an immunoevasive contexture with CD8+ T cell dysfunction and represented an independent predictor for adverse clinical outcomes. Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 970 PTEN 34446716 Melanoma melanoma, colon cancer T cell dysfunction and exhaustion Through counteraction of CD8+ T cell-mediated cytotoxicity, PTENα leads to T cell dysfunction and accelerates immune-resistant cancer progression. Melanoma T_cell_dysfunction_and_exhaustion 971 PTEN 34446716 Colon cancer melanoma, colon cancer T cell dysfunction and exhaustion Through counteraction of CD8+ T cell-mediated cytotoxicity, PTENα leads to T cell dysfunction and accelerates immune-resistant cancer progression. Colon_cancer T_cell_dysfunction_and_exhaustion 972 ARG1 34421926 liver cancer liver cancer T cell dysfunction and exhaustion Immunoregulatory cell populations in the liver, including liver resident dendritic cells (DCs), hepatic stellate cells (HSCs), myeloid-derived suppressor cells (MDSCs), may contribute to intrahepatic CD8+ T cell dysfunction through the production of soluble mediators, such as arginase, indoleamine 2,3-dioxygenase (IDO) and suppressive cytokines and the expression of co-inhibitory molecules. liver_cancer T_cell_dysfunction_and_exhaustion 973 ARG2 34421926 liver cancer liver cancer T cell dysfunction and exhaustion Immunoregulatory cell populations in the liver, including liver resident dendritic cells (DCs), hepatic stellate cells (HSCs), myeloid-derived suppressor cells (MDSCs), may contribute to intrahepatic CD8+ T cell dysfunction through the production of soluble mediators, such as arginase, indoleamine 2,3-dioxygenase (IDO) and suppressive cytokines and the expression of co-inhibitory molecules. liver_cancer T_cell_dysfunction_and_exhaustion 974 IDO1 34421926 liver cancer liver cancer T cell dysfunction and exhaustion Immunoregulatory cell populations in the liver, including liver resident dendritic cells (DCs), hepatic stellate cells (HSCs), myeloid-derived suppressor cells (MDSCs), may contribute to intrahepatic CD8+ T cell dysfunction through the production of soluble mediators, such as arginase, indoleamine 2,3-dioxygenase (IDO) and suppressive cytokines and the expression of co-inhibitory molecules. liver_cancer T_cell_dysfunction_and_exhaustion 975 MAOA 33990379 Melanoma melanoma, colon adenocarcinoma T cell dysfunction and exhaustion Clinical data correlation studies associated intratumoral MAOA expression with T cell dysfunction and decreased patient survival in a broad range of cancers. Melanoma T_cell_dysfunction_and_exhaustion 976 MAOA 33990379 Colon cancer melanoma, colon adenocarcinoma T cell dysfunction and exhaustion Clinical data correlation studies associated intratumoral MAOA expression with T cell dysfunction and decreased patient survival in a broad range of cancers. Colon_cancer T_cell_dysfunction_and_exhaustion 977 OLR1 33959497 Lung cancer non-small cell lung cancer T cell dysfunction and exhaustion In immunotherapy prediction analysis with the comparatively reliable tool TIDE, patients with higher OLR1 expression were predicted to have better immunotherapy outcomes, and OLR1 expression was potentially highly correlated with PD-L1 expression, the average of CD8A and CD8B, IFNG, and Merck18 expression, T cell dysfunction and exclusion potential, and other significant immunotherapy predictors. Lung_cancer T_cell_dysfunction_and_exhaustion 978 GZMB 33312758 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion Furthermore, increased CD103+CD4+ T cells contributed to CD8+T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 979 IFNG 33312758 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion Furthermore, increased CD103+CD4+ T cells contributed to CD8+T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 980 TNF 33312758 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion Furthermore, increased CD103+CD4+ T cells contributed to CD8+T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 981 PRF1 33312758 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion Furthermore, increased CD103+CD4+ T cells contributed to CD8+T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 982 DGKZ 33246984 Colon cancer colorectal cancer T cell dysfunction and exhaustion Our results, which define a role for DGKζ in the control of PD-1 expression, confirm DGKζ potential as a therapeutic target as well as a biomarker of CD8+ T cell dysfunctional states. Colon_cancer T_cell_dysfunction_and_exhaustion 983 PDCD1 33246984 Colon cancer colorectal cancer T cell dysfunction and exhaustion Our results, which define a role for DGKζ in the control of PD-1 expression, confirm DGKζ potential as a therapeutic target as well as a biomarker of CD8+ T cell dysfunctional states. Colon_cancer T_cell_dysfunction_and_exhaustion 984 STING1 33176208 Lung cancer lung cancer T cell dysfunction and exhaustion Treg-dependent immunosuppression triggers effector T cell dysfunction via the STING/ILC2 axis. Lung_cancer T_cell_dysfunction_and_exhaustion 985 HAVCR2 33176208 Lung cancer lung cancer T cell dysfunction and exhaustion Specifically, TIM3+/LAG3+ Tregs prompted Kras-related immunosuppressive chemoresistance and were associated with T cell dysfunction. Lung_cancer T_cell_dysfunction_and_exhaustion 986 LAG3 33176208 Lung cancer lung cancer T cell dysfunction and exhaustion Specifically, TIM3+/LAG3+ Tregs prompted Kras-related immunosuppressive chemoresistance and were associated with T cell dysfunction. Lung_cancer T_cell_dysfunction_and_exhaustion 987 TGFB1 32753468 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion Our data highlight that GC-derived TGF-β1 promotes PD-1 independent CD8+ T cell dysfunction. Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 988 IL10 32200421 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion Moreover, such diffuse type-associated CD8+ T cell dysfunction was featured by elevated expression of immunosuppressive factors including interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1) and indoleamine 2,3-dioxygenase 1 (IDO1). Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 989 TGFB1 32200421 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion Moreover, such diffuse type-associated CD8+ T cell dysfunction was featured by elevated expression of immunosuppressive factors including interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1) and indoleamine 2,3-dioxygenase 1 (IDO1). Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 990 IDO1 32200421 Gastrointestinal cancer gastric cancer T cell dysfunction and exhaustion Moreover, such diffuse type-associated CD8+ T cell dysfunction was featured by elevated expression of immunosuppressive factors including interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1) and indoleamine 2,3-dioxygenase 1 (IDO1). Gastrointestinal_cancer T_cell_dysfunction_and_exhaustion 991 CALM2 32184726 Head and neck cancer head and neck squamous cell carcinoma T cell dysfunction and exhaustion Knockdown of CaM in HD T cells decreased KCa3.1 activity, but not IFNγ production, and reduced their chemotaxis in the presence of adenosine, thus recapitulating HNSCC T cell dysfunction. Head_and_neck_cancer T_cell_dysfunction_and_exhaustion 992 CALM3 32184726 Head and neck cancer head and neck squamous cell carcinoma T cell dysfunction and exhaustion Knockdown of CaM in HD T cells decreased KCa3.1 activity, but not IFNγ production, and reduced their chemotaxis in the presence of adenosine, thus recapitulating HNSCC T cell dysfunction. Head_and_neck_cancer T_cell_dysfunction_and_exhaustion 993 CALM1 32184726 Head and neck cancer head and neck squamous cell carcinoma T cell dysfunction and exhaustion Knockdown of CaM in HD T cells decreased KCa3.1 activity, but not IFNγ production, and reduced their chemotaxis in the presence of adenosine, thus recapitulating HNSCC T cell dysfunction. Head_and_neck_cancer T_cell_dysfunction_and_exhaustion 994 MIR145 31821542 Ovarian cancer ovarian cancer T cell dysfunction and exhaustion Here, we show that cisplatin-mediated miR-145 down-regulation increased PD-L1 expression via targeting the c-Myc transcription factor, thereby inducing T cell apoptosis in vitro. Ovarian_cancer T_cell_dysfunction_and_exhaustion 995 TIGIT 31376919 Leukemia leukemia T cell dysfunction and exhaustion TIGIT expression is upregulated in T cells and causes T cell dysfunction independent of PD-1 and Tim-3 in adult B lineage acute lymphoblastic leukemia. Leukemia T_cell_dysfunction_and_exhaustion 996 AHR 30962630 Brain cancer glioblastoma T cell dysfunction and exhaustion Finally, AHR drives the expression of the ectonucleotidase CD39 in TAMs, which promotes CD8+ T cell dysfunction by producing adenosine in cooperation with CD73. Brain_cancer T_cell_dysfunction_and_exhaustion 997 ENTPD1 30962630 Brain cancer glioblastoma T cell dysfunction and exhaustion Finally, AHR drives the expression of the ectonucleotidase CD39 in TAMs, which promotes CD8+ T cell dysfunction by producing adenosine in cooperation with CD73. Brain_cancer T_cell_dysfunction_and_exhaustion 998 NT5E 30962630 Brain cancer glioblastoma T cell dysfunction and exhaustion Finally, AHR drives the expression of the ectonucleotidase CD39 in TAMs, which promotes CD8+ T cell dysfunction by producing adenosine in cooperation with CD73. Brain_cancer T_cell_dysfunction_and_exhaustion 999 NR4A1 30814730 Lymphoma lymphoma T cell dysfunction and exhaustion This study thus identifies NR4A1 as a key general regulator in the induction of T cell dysfunction, and a potential target for tumour immunotherapy. Lymphoma T_cell_dysfunction_and_exhaustion 1000 NR4A1 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion It has become increasingly clear that several transcriptional factors, including NR4A1, TOX, Eomes, T-bet, Prdm1 (Blimp-1), NFAT and BATF, regulate the PD-1 expression and are implicated in T cell exhaustion and dysfunction。 Pan-cancer T_cell_dysfunction_and_exhaustion 1001 TOX 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion It has become increasingly clear that several transcriptional factors, including NR4A1, TOX, Eomes, T-bet, Prdm1 (Blimp-1), NFAT and BATF, regulate the PD-1 expression and are implicated in T cell exhaustion and dysfunction。 Pan-cancer T_cell_dysfunction_and_exhaustion 1002 EOMES 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion It has become increasingly clear that several transcriptional factors, including NR4A1, TOX, Eomes, T-bet, Prdm1 (Blimp-1), NFAT and BATF, regulate the PD-1 expression and are implicated in T cell exhaustion and dysfunction。 Pan-cancer T_cell_dysfunction_and_exhaustion 1003 TBX21 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion It has become increasingly clear that several transcriptional factors, including NR4A1, TOX, Eomes, T-bet, Prdm1 (Blimp-1), NFAT and BATF, regulate the PD-1 expression and are implicated in T cell exhaustion and dysfunction。 Pan-cancer T_cell_dysfunction_and_exhaustion 1004 PRDM1 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion It has become increasingly clear that several transcriptional factors, including NR4A1, TOX, Eomes, T-bet, Prdm1 (Blimp-1), NFAT and BATF, regulate the PD-1 expression and are implicated in T cell exhaustion and dysfunction。 Pan-cancer T_cell_dysfunction_and_exhaustion 1005 NFATC1 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion It has become increasingly clear that several transcriptional factors, including NR4A1, TOX, Eomes, T-bet, Prdm1 (Blimp-1), NFAT and BATF, regulate the PD-1 expression and are implicated in T cell exhaustion and dysfunction。 Pan-cancer T_cell_dysfunction_and_exhaustion 1006 NFATC2 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion It has become increasingly clear that several transcriptional factors, including NR4A1, TOX, Eomes, T-bet, Prdm1 (Blimp-1), NFAT and BATF, regulate the PD-1 expression and are implicated in T cell exhaustion and dysfunction。 Pan-cancer T_cell_dysfunction_and_exhaustion 1007 BATF 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion It has become increasingly clear that several transcriptional factors, including NR4A1, TOX, Eomes, T-bet, Prdm1 (Blimp-1), NFAT and BATF, regulate the PD-1 expression and are implicated in T cell exhaustion and dysfunction。 Pan-cancer T_cell_dysfunction_and_exhaustion 1008 HIF1A 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion Furthermore, activation of the mTOR pathway and engagement of glycolysis lead to the expression of downstream transcriptional regulators such as HIF-1α and c-Myc, enhancing the expression of inhibitory receptors on T cells. Pan-cancer T_cell_dysfunction_and_exhaustion 1009 MYC 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion Furthermore, activation of the mTOR pathway and engagement of glycolysis lead to the expression of downstream transcriptional regulators such as HIF-1α and c-Myc, enhancing the expression of inhibitory receptors on T cells. Pan-cancer T_cell_dysfunction_and_exhaustion 1010 MTOR 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion Furthermore, activation of the mTOR pathway and engagement of glycolysis lead to the expression of downstream transcriptional regulators such as HIF-1α and c-Myc, enhancing the expression of inhibitory receptors on T cells. Pan-cancer T_cell_dysfunction_and_exhaustion 1011 FOXO1 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion Importantly, FoxO1 sustains PD-1 expression, which promotes the differentiation of terminally exhausted T cells. Pan-cancer T_cell_dysfunction_and_exhaustion 1012 DNMT3A 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion DNA methyltransferase 3A (DNMT3A) has been demonstrated to functionally establish a de novo exhaustion-specific DNA methylation pattern. Inhibition of DNMT3A in these T cells can promote their differentiation toward memory cells. Critically, observations from studies of chronic viral infections indicated a critical role for the demethylation at the promoter region of PD-1 locus in mediating T cell dysfunction. Pan-cancer T_cell_dysfunction_and_exhaustion 1013 TGFB1 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion TGF-β stimulates CD39 and CD73 expression, thereby inhibiting autologous CD8+ T cell proliferation and function. Pan-cancer T_cell_dysfunction_and_exhaustion 1014 IL10 32117960 Pan-cancer review, pan-cancer T cell dysfunction and exhaustion TAMs secret numerous immunosuppressive cytokines and factors, including IL-10, TGF-β and ROS, which induce CD8+ TIL exhaustion and dysfunction. Pan-cancer T_cell_dysfunction_and_exhaustion 1015 FOXP4-AS1 38687433 Other cancers esophageal cancer T cell dysfunction and exhaustion FOXP4-AS1 promotes CD8(+) T cell exhaustion and esophageal cancer immune escape through USP10-stabilized PD-L1. Other_cancers T_cell_dysfunction_and_exhaustion 1016 CMC1 38659649 Melanoma melanoma T cell dysfunction and exhaustion Genetic lost of Cmc1 inhibits the development of CD8+T cell exhaustion in mice. Instead, deletion of Cmc1 in T cells prompts cells to differentiate into metabolically and functionally quiescent cells with increased memory-like features and tolerance to cell death upon repetitive or prolonged T cell receptor (TCR) stimulation. Melanoma T_cell_dysfunction_and_exhaustion 1017 IL1R2 38657120 Breast cancer triple-negative breast cancer T cell dysfunction and exhaustion Here, we observed that IL1R2 blockade strongly attenuated macrophage recruitment and the polarization of tumor-associated macrophages (TAMs) to inhibit BTIC self-renewal and CD8+ T cell exhaustion, which resulted in reduced tumor burden and prolonged survival in TNBC mouse models. Breast_cancer T_cell_dysfunction_and_exhaustion 1018 NOTCH1 38650927 Liver cancer hepatocellular carcinoma T cell dysfunction and exhaustion Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion-a potential target for future immunotherapeutic interventions. Liver_cancer T_cell_dysfunction_and_exhaustion 1019 COL11A1 38649961 Lung cancer lung adenocarcinoma T cell dysfunction and exhaustion COL11A1 may be expressed and secreted by cancer-associated fibroblasts, and a high expression of COL11A1 may result in T cell exhaustion in the tumor microenvironment of lung adenocarcinoma. Lung_cancer T_cell_dysfunction_and_exhaustion 1020 CD58 38635903 Lymphoma diffuse large B-cell lymphoma T cell dysfunction and exhaustion Single-cell RNA sequencing revealed that CD58 expression in tumor cells was negatively correlated with CD8+ T cell exhaustion/dysfunction status. Lymphoma T_cell_dysfunction_and_exhaustion 1021 HNF1A 38590234 Lung cancer lung adenocarcinoma T cell dysfunction and exhaustion Recent studies have highlighted the pivotal roles of T cell transcription factors TCF-1 and TOX in modulating the immune response in cancer, with TCF-1 maintaining CD8+ T cell stemness and TOX promoting T cell exhaustion. Lung_cancer T_cell_dysfunction_and_exhaustion 1022 TOX 38590234 Lung cancer lung adenocarcinoma T cell dysfunction and exhaustion Recent studies have highlighted the pivotal roles of T cell transcription factors TCF-1 and TOX in modulating the immune response in cancer, with TCF-1 maintaining CD8+ T cell stemness and TOX promoting T cell exhaustion. Lung_cancer T_cell_dysfunction_and_exhaustion 1023 TREX1 38489753 Colon cancer colon cancer, breast cancer, and melanoma T cell dysfunction and exhaustion Mechanistically, we show that tumor TREX1 loss drove activation of CD8 T cells and NK cells, prevented CD8 T cell exhaustion, and remodeled an immunosuppressive myeloid compartment. Colon_cancer T_cell_dysfunction_and_exhaustion 1024 TREX1 38489753 Breast cancer colon cancer, breast cancer, and melanoma T cell dysfunction and exhaustion Mechanistically, we show that tumor TREX1 loss drove activation of CD8 T cells and NK cells, prevented CD8 T cell exhaustion, and remodeled an immunosuppressive myeloid compartment. Breast_cancer T_cell_dysfunction_and_exhaustion 1025 TREX1 38489753 Melanoma colon cancer, breast cancer, and melanoma T cell dysfunction and exhaustion Mechanistically, we show that tumor TREX1 loss drove activation of CD8 T cells and NK cells, prevented CD8 T cell exhaustion, and remodeled an immunosuppressive myeloid compartment. Melanoma T_cell_dysfunction_and_exhaustion 1026 LAG3 38480275 Brain cancer glioblastoma T cell dysfunction and exhaustion Lymphocyte-activation gene 3 (LAG-3) binding to human leukocyte antigen-II (HLA-II) plays an essential role in triggering CD4+ T cell exhaustion and could interfere with the efficiency of anti-PD-1 treatment. Brain_cancer T_cell_dysfunction_and_exhaustion 1027 PVR 38324591 Melanoma melanoma T cell dysfunction and exhaustion T cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor (PVR) is an inhibitory immune checkpoint pathway involved in mediating natural killer (NK) cell and T cell exhaustion in tumors. Melanoma T_cell_dysfunction_and_exhaustion 1028 ARID5A 38316094 Colon cancer colorectal cancer T cell dysfunction and exhaustion Our findings revealed that ARID5A upregulation in tumor cells induces T cell exhaustion and immune evasion. Colon_cancer T_cell_dysfunction_and_exhaustion 1029 CD38 38307031 Liver cancer hepatocellular carcinoma T cell dysfunction and exhaustion Collectively, our findings shed light on the role of CD38 in CAR-T cell exhaustion and suggest potential clinical applications of CD38 inhibition in enhancing the efficacy and persistence of CAR-T cell therapy. Liver_cancer T_cell_dysfunction_and_exhaustion 1030 GABPA 38241355 Pan-cancer pan-cancer T cell dysfunction and exhaustion The activation of the NRF2 pathway is negatively correlated with lower T cell infiltration and higher T cell exhaustion. Pan-cancer T_cell_dysfunction_and_exhaustion 1031 SHC3 38175205 Colon cancer colorectal cancer T cell dysfunction and exhaustion Rai upregulation in T cells promoted Programmed cell Death protein (PD)-1 expression and impaired antigen-dependent degranulation of CD8+ T cells by inhibiting phospho-inactivation of glycogen synthase kinase (GSK)-3, a central regulator of PD-1 expression and T cell-mediated anti-tumor immunity. Colon_cancer T_cell_dysfunction_and_exhaustion 1032 FGF21 38309268 Pan-cancer pan-cancer T cell dysfunction and exhaustion Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer T_cell_dysfunction_and_exhaustion 1033 AKT1 38309268 Pan-cancer pan-cancer T cell dysfunction and exhaustion Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer T_cell_dysfunction_and_exhaustion 1034 AKT2 38309268 Pan-cancer pan-cancer T cell dysfunction and exhaustion Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer T_cell_dysfunction_and_exhaustion 1035 AKT3 38309268 Pan-cancer pan-cancer T cell dysfunction and exhaustion Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer T_cell_dysfunction_and_exhaustion 1036 SREBF1 38309268 Pan-cancer pan-cancer T cell dysfunction and exhaustion Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer T_cell_dysfunction_and_exhaustion 1037 MTOR 38309268 Pan-cancer pan-cancer T cell dysfunction and exhaustion Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer T_cell_dysfunction_and_exhaustion 1038 ABCB1 37884430 Pan-cancer review, pan-cancer Metabolic barrier ABC transporters also play a major role in drug bioavailability, and they mediate multidrug resistance in cancer. At least 13 ABC transporters were shown to be involved in drug resistance in vitro. Pan-cancer Metabolic_barrier 1039 NT5E 33927375 Pan-cancer review, pan-cancer Metabolic barrier MDSCs, tumour-associated macrophages (TAMs) and Treg cells produce suppressive metabolites such as adenosine and kynurenine. Adenosine is produced from ATP by the ectoenzymes CD73 and CD39, which are expressed on the surface of these suppressive cells. MDSCs and TAMs produce arginase 1, which utilizes arginine, and indoleamine 2,3-dioxygenase (IDO), which metabolizes tryptophan into suppressive kynurenine, and reduce the availability of these amino acids within the tumour. These mechanisms starve the T cells in the tumour microenvironment of amino acids. Pan-cancer Metabolic_barrier 1040 ENTPD1 33927375 Pan-cancer review, pan-cancer Metabolic barrier MDSCs, tumour-associated macrophages (TAMs) and Treg cells produce suppressive metabolites such as adenosine and kynurenine. Adenosine is produced from ATP by the ectoenzymes CD73 and CD39, which are expressed on the surface of these suppressive cells. MDSCs and TAMs produce arginase 1, which utilizes arginine, and indoleamine 2,3-dioxygenase (IDO), which metabolizes tryptophan into suppressive kynurenine, and reduce the availability of these amino acids within the tumour. These mechanisms starve the T cells in the tumour microenvironment of amino acids. Pan-cancer Metabolic_barrier 1041 ARG1 33927375 Pan-cancer review, pan-cancer Metabolic barrier MDSCs, tumour-associated macrophages (TAMs) and Treg cells produce suppressive metabolites such as adenosine and kynurenine. Adenosine is produced from ATP by the ectoenzymes CD73 and CD39, which are expressed on the surface of these suppressive cells. MDSCs and TAMs produce arginase 1, which utilizes arginine, and indoleamine 2,3-dioxygenase (IDO), which metabolizes tryptophan into suppressive kynurenine, and reduce the availability of these amino acids within the tumour. These mechanisms starve the T cells in the tumour microenvironment of amino acids. Pan-cancer Metabolic_barrier 1042 IDO1 33927375 Pan-cancer review, pan-cancer Metabolic barrier MDSCs, tumour-associated macrophages (TAMs) and Treg cells produce suppressive metabolites such as adenosine and kynurenine. Adenosine is produced from ATP by the ectoenzymes CD73 and CD39, which are expressed on the surface of these suppressive cells. MDSCs and TAMs produce arginase 1, which utilizes arginine, and indoleamine 2,3-dioxygenase (IDO), which metabolizes tryptophan into suppressive kynurenine, and reduce the availability of these amino acids within the tumour. These mechanisms starve the T cells in the tumour microenvironment of amino acids. Pan-cancer Metabolic_barrier 1043 CTLA4 33927375 Pan-cancer review, pan-cancer Metabolic barrier Treg cells exert their immunosuppressive effects through the expression of inhibitory molecules such as CTLA4 and LAG3, as well as by secreting immunosuppressive cytokines such as IL-10, TGFβ and IL-35. CD8+ T cells enter the tumour as PD1− or PD1low cells with intact mitochondria. Pan-cancer Metabolic_barrier 1044 LAG3 33927375 Pan-cancer review, pan-cancer Metabolic barrier Treg cells exert their immunosuppressive effects through the expression of inhibitory molecules such as CTLA4 and LAG3, as well as by secreting immunosuppressive cytokines such as IL-10, TGFβ and IL-35. CD8+ T cells enter the tumour as PD1− or PD1low cells with intact mitochondria. Pan-cancer Metabolic_barrier 1045 IL10 33927375 Pan-cancer review, pan-cancer Metabolic barrier Treg cells exert their immunosuppressive effects through the expression of inhibitory molecules such as CTLA4 and LAG3, as well as by secreting immunosuppressive cytokines such as IL-10, TGFβ and IL-35. CD8+ T cells enter the tumour as PD1− or PD1low cells with intact mitochondria. Pan-cancer Metabolic_barrier 1046 TGFB1 33927375 Pan-cancer review, pan-cancer Metabolic barrier Treg cells exert their immunosuppressive effects through the expression of inhibitory molecules such as CTLA4 and LAG3, as well as by secreting immunosuppressive cytokines such as IL-10, TGFβ and IL-35. CD8+ T cells enter the tumour as PD1− or PD1low cells with intact mitochondria. Pan-cancer Metabolic_barrier 1047 GPM6A 38677545 Pan-cancer review, pan-cancer Metabolic barrier N6-methyladenosine (m6A) RNA methylation modifications have been widely implicated in the metabolic reprogramming of various cell types within the tumor microenvironment (TME) and are essential for meeting the demands of cellular growth and maintaining tissue homeostasis, enabling cells to adapt to the specific conditions of the TME. Pan-cancer Metabolic_barrier 1048 SREBF2 38494433 Gastrointestinal cancer Gastric cancer Metabolic barrier The upregulation of SREBP2 promotes cholesterol metabolism, resulting in alterations in cell membranes, which makes them less susceptible to perforin released by NK cells. Gastrointestinal_cancer Metabolic_barrier 1049 ARG2 38500877 Leukemia leukemia Metabolic barrier Overall, these findings indicate that AML-derived arginase II can lead to the depletion of arginine in the tumor microenvironment, and this in turn might impair T cell proliferation and function. Leukemia Metabolic_barrier 1050 IDO1 38500877 Leukemia leukemia Metabolic barrier IDO catalyzes the degradation of tryptophan into kynurenine resulting in a tryptophan depletion in the tumor microenvironment. The absence of tryptophan as well as elevated levels of kynurenine derivates, namely 3-hydroxykyrunenine and 3-hydroxyanthranilic acid, decrease T cell activation, proliferation, and IFN-γ production. Leukemia Metabolic_barrier 1051 IDH1 38500877 Leukemia leukemia Metabolic barrier R-2-HG is released into the extracellular space and taken up by CD8+ T cells via the transporter SLC13A3. In CD8+ T cells, R-2-HG suppresses aerobic glycolysis, OXPHOS, and polyamine synthesis. Furthermore, R-2-HG reduces the HLA-DP expression on leukemic blasts and dendritic cells. Leukemia Metabolic_barrier 1052 IDH2 38500877 Leukemia leukemia Metabolic barrier R-2-HG is released into the extracellular space and taken up by CD8+ T cells via the transporter SLC13A3. In CD8+ T cells, R-2-HG suppresses aerobic glycolysis, OXPHOS, and polyamine synthesis. Furthermore, R-2-HG reduces the HLA-DP expression on leukemic blasts and dendritic cells. Leukemia Metabolic_barrier 1053 SLC13A3 38500877 Leukemia leukemia Metabolic barrier R-2-HG is released into the extracellular space and taken up by CD8+ T cells via the transporter SLC13A3. In CD8+ T cells, R-2-HG suppresses aerobic glycolysis, OXPHOS, and polyamine synthesis. Furthermore, R-2-HG reduces the HLA-DP expression on leukemic blasts and dendritic cells. Leukemia Metabolic_barrier 1054 STAT5A 38500877 Leukemia leukemia Metabolic barrier Constitutive STAT5 activation results in the transcription of glycolytic genes. Enhanced aerobic glycolysis leads to the accumulation of lactate in the leukemic cell, promoting the nuclear translocation of E3BP and histone lactylation, which induces the transcription of CD274, encoding for PD-L1. Leukemia Metabolic_barrier 1055 STAT5B 38500877 Leukemia leukemia Metabolic barrier Constitutive STAT5 activation results in the transcription of glycolytic genes. Enhanced aerobic glycolysis leads to the accumulation of lactate in the leukemic cell, promoting the nuclear translocation of E3BP and histone lactylation, which induces the transcription of CD274, encoding for PD-L1. Leukemia Metabolic_barrier 1056 PDHX 38500877 Leukemia leukemia Metabolic barrier Constitutive STAT5 activation results in the transcription of glycolytic genes. Enhanced aerobic glycolysis leads to the accumulation of lactate in the leukemic cell, promoting the nuclear translocation of E3BP and histone lactylation, which induces the transcription of CD274, encoding for PD-L1. Leukemia Metabolic_barrier 1057 CD274 38500877 Leukemia leukemia Metabolic barrier Constitutive STAT5 activation results in the transcription of glycolytic genes. Enhanced aerobic glycolysis leads to the accumulation of lactate in the leukemic cell, promoting the nuclear translocation of E3BP and histone lactylation, which induces the transcription of CD274, encoding for PD-L1. Leukemia Metabolic_barrier 1058 CPT1A 38453925 Lung cancer lung cancer Metabolic barrier Significantly, targeting CPT1A enhances immune checkpoint blockade-induced anti-tumor immunity and tumoral ferroptosis in tumor-bearing mice. Lung_cancer Metabolic_barrier 1059 PIK3CB 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1060 PIK3CA 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1061 PIK3CG 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1062 PIK3CD 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1063 PIK3R1 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1064 PIK3R2 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1065 PIK3C3 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1066 PIK3R3 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1067 PIK3C2B 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1068 AKT1 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1069 MTOR 38435444 Leukemia Leukemia Metabolic barrier A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells Leukemia Metabolic_barrier 1070 ALYREF 38402198 Pancreatic cancer pancreatic ductal adenocarcinoma Metabolic barrier ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion. Pancreatic_cancer Metabolic_barrier 1071 JUND 38402198 Pancreatic cancer pancreatic ductal adenocarcinoma Metabolic barrier ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion. Pancreatic_cancer Metabolic_barrier 1072 SLC7A5 38402198 Pancreatic cancer pancreatic ductal adenocarcinoma Metabolic barrier ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion. Pancreatic_cancer Metabolic_barrier 1073 MYC 38390324 Other cancers neuroblastoma Metabolic barrier Prominent interactions have been observed with MYC and HIF-1α, in promoting glucose and glutamine metabolism and activation of antigen presentation on regulatory T cells, and its subsequent metabolic reprogramming. Other_cancers Metabolic_barrier 1074 HIF1A 38390324 Other cancers neuroblastoma Metabolic barrier Prominent interactions have been observed with MYC and HIF-1α, in promoting glucose and glutamine metabolism and activation of antigen presentation on regulatory T cells, and its subsequent metabolic reprogramming. Other_cancers Metabolic_barrier 1075 PABPC1L 38382068 Renal cancer renal cell carcinoma Metabolic barrier PABPC1L bolstered tryptophan metabolism by upregulating IDO1, inducing T-cell dysfunction and Treg infiltration. Renal_cancer Metabolic_barrier 1076 IDO1 38382068 Renal cancer renal cell carcinoma Metabolic barrier PABPC1L bolstered tryptophan metabolism by upregulating IDO1, inducing T-cell dysfunction and Treg infiltration. Renal_cancer Metabolic_barrier 1077 PBX1 38341110 Pan-cancer review, pan-cancer Metabolic barrier Research thus far has corroborated the involvement of PBX1 in cancer proliferation, resisting apoptosis, tumor-associated neoangiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, immune evasion, genome instability, and dysregulating cellular metabolism. Pan-cancer Metabolic_barrier 1078 MIF 38335272 Breast cancer breast cancer Metabolic barrier Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Breast_cancer Metabolic_barrier 1079 WNT5A 38335272 Breast cancer breast cancer Metabolic barrier Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Breast_cancer Metabolic_barrier 1080 WNT3A 38335272 Breast cancer breast cancer Metabolic barrier Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Breast_cancer Metabolic_barrier 1081 WNT4 38335272 Breast cancer breast cancer Metabolic barrier Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Breast_cancer Metabolic_barrier 1082 WNT2 38335272 Breast cancer breast cancer Metabolic barrier Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Breast_cancer Metabolic_barrier 1083 WNT1 38335272 Breast cancer breast cancer Metabolic barrier Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Breast_cancer Metabolic_barrier 1084 WNT7A 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1085 WNT3 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1086 WNT11 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1087 WNT10A 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1088 WNT10B 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1089 WNT16 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1090 WNT2B 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1091 WNT5B 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1092 WNT9B 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1093 WNT6 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1094 WNT9A 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1095 WNT8A 34771718 pan-cancer Review, pan-cancer Metabolic barrier In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. An aberrant WNT/β-catenin pathway has been observed in numerous cancers resulting in the stimulation of numerous WNT target genes involved in tumor initiation, progression and aggressiveness. pan-cancer Metabolic_barrier 1096 CTNNB1 38335272 Breast cancer breast cancer Metabolic barrier Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Breast_cancer Metabolic_barrier 1097 CTNNBIP1 38335272 Breast cancer breast cancer Metabolic barrier Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Breast_cancer Metabolic_barrier 1098 PTPN6 38321204 Leukemia acute myeloid leukemia Metabolic barrier SHP-1 inhibition targets leukaemia stem cells to restore immunosurveillance and enhance chemosensitivity by metabolic reprogramming. Leukemia Metabolic_barrier 1099 PFKP 38321204 Leukemia acute myeloid leukemia Metabolic barrier Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-β-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Leukemia Metabolic_barrier 1100 AKT1 38321204 Leukemia acute myeloid leukemia Metabolic barrier Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-β-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Leukemia Metabolic_barrier 1101 AKT2 38321204 Leukemia acute myeloid leukemia Metabolic barrier Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-β-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Leukemia Metabolic_barrier 1102 AKT3 38321204 Leukemia acute myeloid leukemia Metabolic barrier Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-β-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Leukemia Metabolic_barrier 1103 CTNNB1 38321204 Leukemia acute myeloid leukemia Metabolic barrier Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-β-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Leukemia Metabolic_barrier 1104 FGF21 38309268 Pan-cancer pan-cancer Metabolic barrier Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8(+)T cells. Pan-cancer Metabolic_barrier 1105 SREBF1 38309268 Pan-cancer pan-cancer Metabolic barrier Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer Metabolic_barrier 1106 AKT1 38309268 Pan-cancer pan-cancer Metabolic barrier Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer Metabolic_barrier 1107 AKT2 38309268 Pan-cancer pan-cancer Metabolic barrier Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer Metabolic_barrier 1108 AKT3 38309268 Pan-cancer pan-cancer Metabolic barrier Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer Metabolic_barrier 1109 MTOR 38309268 Pan-cancer pan-cancer Metabolic barrier Mechanistically, FGF21 sustains the hyperactivation of AKT-mTORC1-sterol regulatory-element-binding protein 1 (SREBP1) signal axis in the activated CD8+T cells, resulting in the augment of cholesterol biosynthesis and T cell exhaustion. Pan-cancer Metabolic_barrier 1110 TRIB3 38235126 Head and neck cancer head and neck squamous cell carcinoma Metabolic barrier As a pseudokinase, Tribbles Pseudokinase 3 (TRIB3) is implicated in a wide array of biological processes, including cell signal transduction, metabolic regulation, stress responses, and immune regulation. TRIB3 could serve as a potential prognostic marker for HNSC and might be a key gene mediating HNSC immune evasion. Head_and_neck_cancer Metabolic_barrier 1111 YTHDF1 38202722 Pan-cancer pan-cancer Metabolic barrier YTHDF1 serves as a pivotal member, playing a crucial role in protein translation, tumor proliferation, metabolic reprogramming of various tumor cells, and immune evasion. Pan-cancer Metabolic_barrier 1112 NFX1 38177283 Liver cancer hepatocellular carcinoma Metabolic barrier Carnosine maintains intracellular pH (pHi) homeostasis by functioning as a mobile proton carrier to accelerate cytosolic H+ mobility and release, which in turn controls lysosomal subcellular distribution, acidification and activity. Furthermore, by maintaining lysosomal activity, carnosine facilitates nuclear transcription factor X-box binding 1 (NFX1) degradation, triggering galectin-9 and T-cell-mediated immune escape and tumorigenesis. Liver_cancer Metabolic_barrier 1113 LGALS9 38177283 Liver cancer hepatocellular carcinoma Metabolic barrier Carnosine maintains intracellular pH (pHi) homeostasis by functioning as a mobile proton carrier to accelerate cytosolic H+ mobility and release, which in turn controls lysosomal subcellular distribution, acidification and activity. Furthermore, by maintaining lysosomal activity, carnosine facilitates nuclear transcription factor X-box binding 1 (NFX1) degradation, triggering galectin-9 and T-cell-mediated immune escape and tumorigenesis. Liver_cancer Metabolic_barrier 1114 TNFSF10 38157648 Other cancers cervical cancer Metabolic barrier TRAIL-driven targeting and reversing cervical cancer radioresistance by seleno-nanotherapeutics through regulating cell metabolism. Other_cancers Metabolic_barrier 1115 ALDH2 38088186 Breast cancer breast cancer Metabolic barrier Mechanistically, inhibiting ALDH2-mediated metabolism of aldehyde downregulated the expression of V-domain Ig suppressor of T-cell activation (VISTA) via inactivating the nucleotide oligomerization domain (NOD)/nuclear factor kappa-B (NF-κB) signaling pathway. Breast_cancer Metabolic_barrier 1116 NFKB1 38088186 Breast cancer breast cancer Metabolic barrier Mechanistically, inhibiting ALDH2-mediated metabolism of aldehyde downregulated the expression of V-domain Ig suppressor of T-cell activation (VISTA) via inactivating the nucleotide oligomerization domain (NOD)/nuclear factor kappa-B (NF-κB) signaling pathway. Breast_cancer Metabolic_barrier 1117 NOD1 38088186 Breast cancer breast cancer Metabolic barrier Mechanistically, inhibiting ALDH2-mediated metabolism of aldehyde downregulated the expression of V-domain Ig suppressor of T-cell activation (VISTA) via inactivating the nucleotide oligomerization domain (NOD)/nuclear factor kappa-B (NF-κB) signaling pathway. Breast_cancer Metabolic_barrier 1118 BSG 38023152 Pan-cancer pan-cancer Metabolic barrier CD147 is integral to the diverse but complimentary hallmarks of cancer: it is pivotal in cancerous proliferative signaling, growth propagation, cellular survival, replicative immortality, angiogenesis, metabolic reprogramming, immune evasion, invasion, and metastasis. Pan-cancer Metabolic_barrier 1119 HMGB1 37986958 Lung cancer non-small cell lung adenocarcinoma Metabolic barrier Unsaturated fatty acid alters the immune response in non-small cell lung adenocarcinoma through regulation of HMGB1 trafficking. Lung_cancer Metabolic_barrier 1120 PIK3CA 37965796 Breast cancer luminal breast cancer Metabolic barrier Oncogenic PIK3CA mutations (PIK3CAmut ) frequently occur in a higher proportion in luminal breast cancer (LBC), especially in refractory advanced cases, and are associated with changes in tumour cellular metabolism. Breast_cancer Metabolic_barrier 1121 ALOX5 37965796 Breast cancer luminal breast cancer Metabolic barrier Mechanistically, PIK3CAmut activates the transcription of 5-lipoxygenase (5-LOX) in a STAT3-dependent manner, which in turn directly results in high LTB4 production, binding to BLT2 on MDSCs and promoting their infiltration. Breast_cancer Metabolic_barrier 1122 STAT3 37965796 Breast cancer luminal breast cancer Metabolic barrier Mechanistically, PIK3CAmut activates the transcription of 5-lipoxygenase (5-LOX) in a STAT3-dependent manner, which in turn directly results in high LTB4 production, binding to BLT2 on MDSCs and promoting their infiltration. Breast_cancer Metabolic_barrier 1123 LTB4R2 37965796 Breast cancer luminal breast cancer Metabolic barrier Mechanistically, PIK3CAmut activates the transcription of 5-lipoxygenase (5-LOX) in a STAT3-dependent manner, which in turn directly results in high LTB4 production, binding to BLT2 on MDSCs and promoting their infiltration. Breast_cancer Metabolic_barrier 1124 CXCL8 37963015 Prostate cancer prostate cancer Metabolic barrier Prostate cancer cell-derived exosomal IL-8 fosters immune evasion by disturbing glucolipid metabolism of CD8(+) T cell. Prostate_cancer Metabolic_barrier 1125 PPARA 37963015 Prostate cancer prostate cancer Metabolic barrier Mechanistically, exosomal IL-8 overactivated PPARα in recipient cells, thereby decreasing glucose utilization by downregulating GLUT1 and HK2 but increasing fatty acid catabolism via upregulation of CPT1A and ACOX1. PPARα further activates uncoupling protein 1 (UCP1), leading to fatty acid catabolism for thermogenesis rather than ATP synthesis. Prostate_cancer Metabolic_barrier 1126 SLC2A1 37963015 Prostate cancer prostate cancer Metabolic barrier Mechanistically, exosomal IL-8 overactivated PPARα in recipient cells, thereby decreasing glucose utilization by downregulating GLUT1 and HK2 but increasing fatty acid catabolism via upregulation of CPT1A and ACOX1. PPARα further activates uncoupling protein 1 (UCP1), leading to fatty acid catabolism for thermogenesis rather than ATP synthesis. Prostate_cancer Metabolic_barrier 1127 ACOX1 37963015 Prostate cancer prostate cancer Metabolic barrier Mechanistically, exosomal IL-8 overactivated PPARα in recipient cells, thereby decreasing glucose utilization by downregulating GLUT1 and HK2 but increasing fatty acid catabolism via upregulation of CPT1A and ACOX1. PPARα further activates uncoupling protein 1 (UCP1), leading to fatty acid catabolism for thermogenesis rather than ATP synthesis. Prostate_cancer Metabolic_barrier 1128 UCP1 37963015 Prostate cancer prostate cancer Metabolic barrier Mechanistically, exosomal IL-8 overactivated PPARα in recipient cells, thereby decreasing glucose utilization by downregulating GLUT1 and HK2 but increasing fatty acid catabolism via upregulation of CPT1A and ACOX1. PPARα further activates uncoupling protein 1 (UCP1), leading to fatty acid catabolism for thermogenesis rather than ATP synthesis. Prostate_cancer Metabolic_barrier 1129 G3BP1 37913942 Pan-cancer pan-cancer Metabolic barrier Cancer cells face various stress conditions in tumor microenvironment during tumorigenesis, while SGs contribute to hallmarks of cancer including proliferation, invasion, migration, avoiding apoptosis, metabolism reprogramming and immune evasion. Pan-cancer Metabolic_barrier 1130 NT5E 37891562 Pan-cancer pan-cancer Metabolic barrier Methotrexate (MTX) is a common chemotherapeutic drug that inhibits DNA synthesis and induces apoptosis. Treatment with MTX increased CD73 expression, which leads to higher levels of extracellular adenosine. Adenosine levels are also high in the tumor microenvironment through Cancer cells metabolism. That promotes the survival of cancer cells and contributes to tumor immune evasion through the Adenosine 2a Receptor. Pan-cancer Metabolic_barrier 1131 ADORA2A 37891562 Pan-cancer pan-cancer Metabolic barrier Methotrexate (MTX) is a common chemotherapeutic drug that inhibits DNA synthesis and induces apoptosis. Treatment with MTX increased CD73 expression, which leads to higher levels of extracellular adenosine. Adenosine levels are also high in the tumor microenvironment through Cancer cells metabolism. That promotes the survival of cancer cells and contributes to tumor immune evasion through the Adenosine 2a Receptor. Pan-cancer Metabolic_barrier 1132 METTL3 37889223 Leukemia human acute myeloid leukemia Metabolic barrier The m6A level is dynamically regulated by RNA epigenetic machinery comprising methyltransferases such as methyltransferase-like protein 3 (METTL3), demethylases FTO and AlkB human homologue 5 (ALKBH5), and multiple reader proteins. The m6A modification influences nearly every step of RNA metabolism and thus broadly affects gene expression at multiple levels, playing a critical role in many biological processes, including cancer progression, metastasis, and immune evasion. Leukemia Metabolic_barrier 1133 ALKBH5 37889223 Leukemia human acute myeloid leukemia Metabolic barrier The m6A level is dynamically regulated by RNA epigenetic machinery comprising methyltransferases such as methyltransferase-like protein 3 (METTL3), demethylases FTO and AlkB human homologue 5 (ALKBH5), and multiple reader proteins. The m6A modification influences nearly every step of RNA metabolism and thus broadly affects gene expression at multiple levels, playing a critical role in many biological processes, including cancer progression, metastasis, and immune evasion. Leukemia Metabolic_barrier 1134 ONECUT3 37875589 Pancreatic cancer Pancreatic ductal adenocarcinoma Metabolic barrier Our study reveals ONECUT3 as a candidate stemness-related transcription factor regulating NK cell-targeted inhibitory immune checkpoints in PDAC. ONECUT3-mediated prostanoid metabolism may regulate cancer stemness and immune evasion in PDAC Pancreatic_cancer Metabolic_barrier 1135 TERT 37863351 Pan-cancer pan-cancer Metabolic barrier Telomere reverse transcriptase (TERT), has been found to interact with various signaling molecules like cMYC, NF-kB, BRG1 and cooperate in transcription and metabolic reprogramming, acting as a strong proponent of malignant features such as cell death resistance, sustained proliferation, angiogenesis activation, and metastasis, among others. Pan-cancer Metabolic_barrier 1136 MYC 37833558 liver cancer liver cancer Metabolic barrier In liver cancer, MYC and its signaling pathways undergo significant changes, exerting a profound impact on liver cancer progression, including tumor proliferation, metastasis, dedifferentiation, metabolism, immune microenvironment, and resistance to comprehensive therapies. liver_cancer Metabolic_barrier 1137 CD276 37768439 Colon cancer colorectal cancer Metabolic barrier B7-H3 compliment CRC progression by regulating glucose metabolism, and the abnormal level of metabolites secreted influence the type and function of the immune cells in the TME, further promoting chemoresistance. B7-H3 has been documented as a critical immune-independent contributor to cancer glucose metabolism reprogramming via ROS-mediated stabilization of HIF-1α. Colon_cancer Metabolic_barrier 1138 HIF1A 37768439 Colon cancer colorectal cancer Metabolic barrier B7-H3 compliment CRC progression by regulating glucose metabolism, and the abnormal level of metabolites secreted influence the type and function of the immune cells in the TME, further promoting chemoresistance. B7-H3 has been documented as a critical immune-independent contributor to cancer glucose metabolism reprogramming via ROS-mediated stabilization of HIF-1α. Colon_cancer Metabolic_barrier 1139 IDO1 37756581 Lung cancer Non-Small Cell Lung Cancer Metabolic barrier Overexpression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) has been reported in several tumor types, including non-small cell lung cancer (NSCLC), and has been shown to promote tumor-immune evasion and inhibit T-cell activation through increased tryptophan degradation and the production of several immunosuppressive metabolites collectively known as kynurenines. Lung_cancer Metabolic_barrier 1140 NFE2L2 37716475 Head and neck cancer head and neck squamous cell carcinoma Metabolic barrier The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, and chemoradiation resistance. Head_and_neck_cancer Metabolic_barrier 1141 STK11 37675220 Lung cancer non-small cell lung cancer Metabolic barrier NSCLC tumors that have two alterations in tumor suppressor genes, such as liver kinase B1 (LKB1) and/or Kelch-like ECH-associated protein 1 (KEAP1), have been found to exhibit reduced responsiveness to these therapeutic strategies, as revealed by multiomics analyses identifying immunosuppressed phenotypes. Lung_cancer Metabolic_barrier 1142 KEAP1 37675220 Lung cancer non-small cell lung cancer Metabolic barrier NSCLC tumors that have two alterations in tumor suppressor genes, such as liver kinase B1 (LKB1) and/or Kelch-like ECH-associated protein 1 (KEAP1), have been found to exhibit reduced responsiveness to these therapeutic strategies, as revealed by multiomics analyses identifying immunosuppressed phenotypes. Lung_cancer Metabolic_barrier 1143 LILRB2 37622462 Breast cancer Triple-negative breast cancer Metabolic barrier Further mechanistic analysis revealed that ILT4 reprogrammed aerobic glycolysis of tumor cells via AKT-mTOR signaling-mediated glucose transporter 3 (GLUT3; also known as SLC2A3) and pyruvate kinase muscle 2 (PKM2, an isoform encoded by PKM) overexpression. ILT4 inhibition in TNBC reduced tumor progression and GLUT3 and PKM2 expression in vivo. Breast_cancer Metabolic_barrier 1144 AKT1 37622462 Breast cancer Triple-negative breast cancer Metabolic barrier Further mechanistic analysis revealed that ILT4 reprogrammed aerobic glycolysis of tumor cells via AKT-mTOR signaling-mediated glucose transporter 3 (GLUT3; also known as SLC2A3) and pyruvate kinase muscle 2 (PKM2, an isoform encoded by PKM) overexpression. ILT4 inhibition in TNBC reduced tumor progression and GLUT3 and PKM2 expression in vivo. Breast_cancer Metabolic_barrier 1145 AKT2 37622462 Breast cancer Triple-negative breast cancer Metabolic barrier Further mechanistic analysis revealed that ILT4 reprogrammed aerobic glycolysis of tumor cells via AKT-mTOR signaling-mediated glucose transporter 3 (GLUT3; also known as SLC2A3) and pyruvate kinase muscle 2 (PKM2, an isoform encoded by PKM) overexpression. ILT4 inhibition in TNBC reduced tumor progression and GLUT3 and PKM2 expression in vivo. Breast_cancer Metabolic_barrier 1146 AKT3 37622462 Breast cancer Triple-negative breast cancer Metabolic barrier Further mechanistic analysis revealed that ILT4 reprogrammed aerobic glycolysis of tumor cells via AKT-mTOR signaling-mediated glucose transporter 3 (GLUT3; also known as SLC2A3) and pyruvate kinase muscle 2 (PKM2, an isoform encoded by PKM) overexpression. ILT4 inhibition in TNBC reduced tumor progression and GLUT3 and PKM2 expression in vivo. Breast_cancer Metabolic_barrier 1147 MTOR 37622462 Breast cancer Triple-negative breast cancer Metabolic barrier Further mechanistic analysis revealed that ILT4 reprogrammed aerobic glycolysis of tumor cells via AKT-mTOR signaling-mediated glucose transporter 3 (GLUT3; also known as SLC2A3) and pyruvate kinase muscle 2 (PKM2, an isoform encoded by PKM) overexpression. ILT4 inhibition in TNBC reduced tumor progression and GLUT3 and PKM2 expression in vivo. Breast_cancer Metabolic_barrier 1148 FTO 37526345 Renal cancer Renal Cell Carcinoma Metabolic barrier In this study, a significant decrease is found in the abundance of alpha-ketoglutarate (αKG), a crucial intermediate metabolite in the TCA cycle, which is correlated with higher grades and a worse prognosis in clinical RCC samples. Renal_cancer Metabolic_barrier 1149 SLC2A1 37506695 Pan-cancer pan-cancer Metabolic barrier Mechanistically, Glut1 inactivation causes metabolic rewiring toward oxidative phosphorylation, which generates an excessive amount of reactive oxygen species (ROS). Accumulated ROS potentiate tumor cell death mediated by tumor necrosis factor alpha (TNF-α) in a caspase-8- and Fadd-dependent manner. Pan-cancer Metabolic_barrier 1150 STING1 37443289 Colon cancer colorectal carcinoma Metabolic barrier Mechanistically, STING targets hexokinase II (HK2) to block its hexokinase activity. As such, STING inhibits HK2 to restrict tumour aerobic glycolysis and promote antitumour immunity in vivo. In human colorectal carcinoma samples, lactate, which can be used as a surrogate for aerobic glycolysis, is negatively correlated with STING expression level and antitumour immunity. Colon_cancer Metabolic_barrier 1151 HK2 37443289 Colon cancer colorectal carcinoma Metabolic barrier Mechanistically, STING targets hexokinase II (HK2) to block its hexokinase activity. As such, STING inhibits HK2 to restrict tumour aerobic glycolysis and promote antitumour immunity in vivo. In human colorectal carcinoma samples, lactate, which can be used as a surrogate for aerobic glycolysis, is negatively correlated with STING expression level and antitumour immunity. Colon_cancer Metabolic_barrier 1152 CDCA4 37304553 Liver cancer hepatocellular carcinoma Metabolic barrier The gene set enrichment analysis (GSEA) suggested that CDCA4 mainly affected the biological events of LIHC by participating in the cell cycle, T cell receptor signaling pathway, DNA replication, glucose metabolism, and mitogen activated protein kinase (MAPK) signaling pathway. Liver_cancer Metabolic_barrier 1153 PIGL 37280393 Liver cancer hepatocellular carcinoma Metabolic barrier Specifically, nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20, which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells. Liver_cancer Metabolic_barrier 1154 BRD4 37280393 Liver cancer hepatocellular carcinoma Metabolic barrier Specifically, nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20, which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells. Liver_cancer Metabolic_barrier 1155 MYC 37280393 Liver cancer hepatocellular carcinoma Metabolic barrier Specifically, nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20, which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells. Liver_cancer Metabolic_barrier 1156 CCL2 37280393 Liver cancer hepatocellular carcinoma Metabolic barrier Specifically, nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20, which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells. Liver_cancer Metabolic_barrier 1157 CCL20 37280393 Liver cancer hepatocellular carcinoma Metabolic barrier Specifically, nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20, which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells. Liver_cancer Metabolic_barrier 1158 FAS 37256177 Pan-cancer pan-cancer Metabolic barrier The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Pan-cancer Metabolic_barrier 1159 ADA 37253111 Colon cancer colorectal cancer Metabolic barrier In an in silico screen, we identified ADA and PDK1 as metabolic regulators. We then showed that overexpression (OE) of these genes enhanced the cytolysis of CD19-specific chimeric antigen receptor (CAR) T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampened this effect. Colon_cancer Metabolic_barrier 1160 PDK1 37253111 Colon cancer colorectal cancer Metabolic barrier In an in silico screen, we identified ADA and PDK1 as metabolic regulators. We then showed that overexpression (OE) of these genes enhanced the cytolysis of CD19-specific chimeric antigen receptor (CAR) T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampened this effect. Colon_cancer Metabolic_barrier 1161 MAT1A 37236192 Breast cancer breast cancer Metabolic barrier By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Breast_cancer Metabolic_barrier 1162 FASN 37236192 Breast cancer breast cancer Metabolic barrier By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Breast_cancer Metabolic_barrier 1163 HLA-DRB1 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1164 HLA-DQB1 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1165 HLA-DQA1 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1166 HLA-DPB1 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1167 HLA-DRA 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1168 HLA-DRB5 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1169 HLA-DRB3 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1170 HLA-DRB4 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1171 HLA-DPA1 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1172 HLA-DMB 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1173 HLA-DMA 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1174 HLA-DOA 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1175 HLA-DQA2 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1176 HLA-DQB2 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1177 HLA-DOB 32367803 Pan-cancer Review, pan-cancer Metabolic barrier Metabolic reprogramming from catabolism to anabolism is initiated upon T Cell Receptor (TCR) recognition of cognate antigen presented on major histocompatibility complex (MHC) and with the help of CD28-mediated co-stimulation. Pan-cancer Metabolic_barrier 1178 RIPK3 37150500 Pan-cancer pan-cancer Metabolic barrier Our findings demonstrate that RIPK3 deficiency leads to cholesterol abrogation in MDSCs, which facilitates tumor-infiltrating MDSC activation, and highlight the therapeutic potential of targeting cholesterol synthesis to overcome tumor immune evasion. Pan-cancer Metabolic_barrier 1179 MYC 37119690 Colon cancer colorectal cancer Metabolic barrier Elevated Myc promotes stress adaptation, metabolic reprogramming, and immune evasion to drive cancer development and therapeutic resistance through broad changes in transcriptional and translational landscapes. Colon_cancer Metabolic_barrier 1180 SBSN 36896786 Oral cancer oral squamous cell carcinoma Metabolic barrier SBSN increased cell invasion more under hypoxia than under normoxia, and this resulted from increased cell migration, not from matrix metalloprotease activity or epithelial‑mesenchymal transition. Furthermore, SBSN induced angiogenesis more strongly under hypoxia than under normoxia. These results demonstrated the importance of SBSN in the maintenance of survival and proliferation, invasion and angiogenesis of OSCC cells under hypoxia. Oral_cancer Metabolic_barrier 1181 STEAP4 37101765 Liver cancer hepatocellular carcinoma Metabolic barrier Furthermore, reduced STEAP4 expression was a significant predictor of worse RFS in univariate and multivariate analyses in the immunohistochemical cohort. GO, KEGG, and GSEA analyses revealed that STEAP4 is related to numerous biological processes and pathways, including drug metabolism, DNA replication, RNA metabolism, and immune response. In terms of the immune system, the decreased level of STEAP4 was correlated with the immunosuppressive microenvironment. Liver_cancer Metabolic_barrier 1182 FAS 30830880 Pan-cancer pan-cancer Inducing apoptosis of CTLs The apoptosis-inducing ligand FasL is preferentially expressed on tumor cells. T cells used for adoptive immunotherapy constitutively express Fas, the receptor for FasL. Cognate Fas-FasL interaction limits T cell persistence and ultimately affects antitumor efficacy. Pan-cancer Inducing_apoptosis_of_CTLs 1183 FASLG 30830880 Pan-cancer pan-cancer Inducing apoptosis of CTLs The apoptosis-inducing ligand FasL is preferentially expressed on tumor cells. T cells used for adoptive immunotherapy constitutively express Fas, the receptor for FasL. Cognate Fas-FasL interaction limits T cell persistence and ultimately affects antitumor efficacy. Pan-cancer Inducing_apoptosis_of_CTLs 1184 NACC1 36150745 Melanoma melanoma Inducing apoptosis of CTLs NAC1 positively regulated the expression of LDHA at the transcriptional level, which led to higher accumulation of lactic acid in the TME. This inhibited the cytokine production and induced exhaustion and apoptosis of CTLs, impairing their cell-killing ability. Melanoma Inducing_apoptosis_of_CTLs 1185 LDHA 36150745 Melanoma melanoma Inducing apoptosis of CTLs NAC1 positively regulated the expression of LDHA at the transcriptional level, which led to higher accumulation of lactic acid in the TME. This inhibited the cytokine production and induced exhaustion and apoptosis of CTLs, impairing their cell-killing ability. Melanoma Inducing_apoptosis_of_CTLs 1186 NKILA 30224822 Breast cancer breast cancer Inducing apoptosis of CTLs Clinically, NKILA overexpression in tumor-specific CTLs and TH1 cells correlated with their apoptosis and shorter patient survival. Breast_cancer Inducing_apoptosis_of_CTLs 1187 CPT1A 30143538 Colon cancer colon carcinoma Inducing apoptosis of CTLs Bezafibrate also increased fatty acid oxidation (FAO) and mitochondrial respiratory capacity, which supports the extra energy demands of cells in emergencies, allowing cell survival. Carnitine palmitoyl transferase 1 (Cpt1), which is needed for FAO, and Bcl2 were both upregulated. Cpt1 and Bcl2 can form a complex to prevent apoptosis of CTLs. Colon_cancer Inducing_apoptosis_of_CTLs 1188 BCL2 30143538 Colon cancer colon carcinoma Inducing apoptosis of CTLs Bezafibrate also increased fatty acid oxidation (FAO) and mitochondrial respiratory capacity, which supports the extra energy demands of cells in emergencies, allowing cell survival. Carnitine palmitoyl transferase 1 (Cpt1), which is needed for FAO, and Bcl2 were both upregulated. Cpt1 and Bcl2 can form a complex to prevent apoptosis of CTLs. Colon_cancer Inducing_apoptosis_of_CTLs 1189 PRF1 28096300 Lung cancer lung cancer. Inducing apoptosis of CTLs Moreover, CD8+25+ Tregs inhibit CTLs through inducing CTL death via perforin-mediated apoptosis and through reducing effector CTL cytotoxic activity via down-regulating CTL perforin-production and degranulation. Lung_cancer Inducing_apoptosis_of_CTLs 1190 MUC4 24534824 Pancreatic cancer pancreatic cancer Inducing apoptosis of CTLs The results demonstrated that the level of MUC4 membrane expression strongly positively correlated with MS-CTL apoptosis and the influence of supernatants and Fas-blockade did not significantly correlate with MS-CTL apoptosis. This evidence suggested that there may be a novel counterattack pathway of pancreatic cancer cells, which is a MUC4-mediated, cell contact-dependent and Fas-independent process, to induce CTL apoptosis. Pancreatic_cancer Inducing_apoptosis_of_CTLs 1191 CD274 24336068 Breast cancer breast cancer Inducing apoptosis of CTLs We found that higher expression of PD-L1 induced in tumor cells by exposure to hypoxia led to increased apoptosis of cocultured CTLs and Jurkat leukemia T cells. Breast_cancer Inducing_apoptosis_of_CTLs 1192 IRF8 23677993 Breast cancer breast and colorectal cancer Inducing apoptosis of CTLs Our data thus determined that MDSCs use down-regulation of IRF8 to alter Bax and Bcl-xL expression to deregulate the Fas-mediated apoptosis pathway to evade elimination by host CTLs. Breast_cancer Inducing_apoptosis_of_CTLs 1193 IRF8 23677993 Colon cancer breast and colorectal cancer Inducing apoptosis of CTLs Our data thus determined that MDSCs use down-regulation of IRF8 to alter Bax and Bcl-xL expression to deregulate the Fas-mediated apoptosis pathway to evade elimination by host CTLs. Colon_cancer Inducing_apoptosis_of_CTLs 1194 BAX 23677993 Breast cancer breast and colorectal cancer Inducing apoptosis of CTLs Our data thus determined that MDSCs use down-regulation of IRF8 to alter Bax and Bcl-xL expression to deregulate the Fas-mediated apoptosis pathway to evade elimination by host CTLs. Breast_cancer Inducing_apoptosis_of_CTLs 1195 BAX 23677993 Colon cancer breast and colorectal cancer Inducing apoptosis of CTLs Our data thus determined that MDSCs use down-regulation of IRF8 to alter Bax and Bcl-xL expression to deregulate the Fas-mediated apoptosis pathway to evade elimination by host CTLs. Colon_cancer Inducing_apoptosis_of_CTLs 1196 BCL2L1 23677993 Breast cancer breast and colorectal cancer Inducing apoptosis of CTLs Our data thus determined that MDSCs use down-regulation of IRF8 to alter Bax and Bcl-xL expression to deregulate the Fas-mediated apoptosis pathway to evade elimination by host CTLs. Breast_cancer Inducing_apoptosis_of_CTLs 1197 BCL2L1 23677993 Colon cancer breast and colorectal cancer Inducing apoptosis of CTLs Our data thus determined that MDSCs use down-regulation of IRF8 to alter Bax and Bcl-xL expression to deregulate the Fas-mediated apoptosis pathway to evade elimination by host CTLs. Colon_cancer Inducing_apoptosis_of_CTLs 1198 FOLH1 23295983 Prostate cancer prostate cancer Inducing apoptosis of CTLs Results showed that tPSMA gene-pulsed DCs effectively induced T lymphocyte activation and cytotoxicity, which was enhanced by upregulated expression of 4-1BBL, displaying better cell viability, lower CTLs apoptosis, higher expression anti-apoptotic protein of Bcl-xL and phosphorylation of P38, enhanced NF-κB activation, as well as more IFN-γ production. Prostate_cancer Inducing_apoptosis_of_CTLs