biostudies-literatureXing ZNational Key R&D Program of ChinaNational Key R&D Program of China870https://www.ebi.ac.uk/biostudies/studies/S-EPMC11279595biostudies-literatureUnknown16(7)Glioma is characterized by strong immunosuppression and excessive angiogenesis. Based on existing reports, it can be speculated that the resistance to anti-angiogenic drug vascular endothelial growth factor A (VEGFA) antibody correlates to the induction of novel immune checkpoint indoleamine 2,3-dioxygenase 1 (IDO1), while IDO1 has also been suggested to be related to tumor angiogenesis. Herein, we aim to clarify the potential role of IDO1 in glioma angiogenesis and the mechanism behind it. Bioinformatic analyses showed that the expressions of IDO1 and angiogenesis markers VEGFA and CD34 were positively correlated and increased with pathological grade in glioma. IDO1-overexpression-derived-tryptophan depletion activated the general control nonderepressible 2 (GCN2) pathway and upregulated PharmaceuticsIDO1 Inhibitor RY103 Suppresses Trp-GCN2-Mediated Angiogenesis and Counters Immunosuppression in Glioblastoma.PMC112795952021YFC27018052021YFC2701800Xing ZLi XHe ZNTFang XLiang HKuang CLi AYang QfalseIDO1 Inhibitor RY103 Suppresses Trp-GCN2-Mediated Angiogenesis and Counters Immunosuppression in Glioblastoma.Glioma is characterized by strong immunosuppression and excessive angiogenesis. Based on existing reports, it can be speculated that the resistance to anti-angiogenic drug vascular endothelial growth factor A (VEGFA) antibody correlates to the induction of novel immune checkpoint indoleamine 2,3-dioxygenase 1 (IDO1), while IDO1 has also been suggested to be related to tumor angiogenesis. Herein, we aim to clarify the potential role of IDO1 in glioma angiogenesis and the mechanism behind it. Bioinformatic analyses showed that the expressions of IDO1 and angiogenesis markers VEGFA and CD34 were positively correlated and increased with pathological grade in glioma. IDO1-overexpression-derived-tryptophan depletion activated the general control nonderepressible 2 (GCN2) pathway and upregulated 2024-01-01T00:00:00Z2024 Jun2026-04-21T03:24:21.923Z2025-04-19T13:10:44.813ZS-EPMC112795953906556710.3390/pharmaceutics16070870