Indoleamine 2,3‐dioxygenase 1 inhibition reverses cancer‐associated fibroblast‐mediated immunosuppression in high‐grade serous ovarian cancer

Cancer‐associated fibroblasts (CAFs) contribute to immunosuppression in the ovarian cancer microenvironment, partly through upregulation of indoleamine 2,3‐dioxygenase 1 (IDO1). This study examined CAF‐mediated suppression of T‐cell function and the potential of IDO1 inhibition to reverse these effects. CAFs from high‐grade serous ovarian cancer (HGSOC) patients exhibited increased IDO1, COX2, and PD‐L1 expression upon interaction with activated T cells, along with elevated immunosuppressive cytokines. CAFs suppressed T‐cell proliferation and induced PD‐1 expression in CD4+ and CD8+ T cells, effects reversed by epacadostat. IDO1 inhibition enhanced T‐cell proliferation via AKT signaling, restored T‐cell cytotoxicity, and increased ovarian cancer cell apoptosis. These findings suggest that targeting IDO1 may help counteract CAF‐mediated immunosuppression and enhance antitumor immunity in HGSOC.