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.