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

## TL;DR

Inhibiting IDO1 reverses immunosuppression caused by cancer-associated fibroblasts in high-grade serous ovarian cancer, restoring T-cell function and increasing cancer cell death.

## Contribution

This study demonstrates that IDO1 inhibition can reverse CAF-mediated immunosuppression in ovarian cancer.

## Key findings

- CAF-mediated suppression of T-cell proliferation and PD-1 expression is reversed by IDO1 inhibition.
- IDO1 inhibition enhances T-cell cytotoxicity and increases ovarian cancer cell apoptosis.
- IDO1 inhibition restores T-cell function via AKT signaling.

## Abstract

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.

CAF‐mediated immunosuppression in ovarian cancer is driven by IDO1, reducing T‐cell function. Inhibiting IDO1 restores T‐cell proliferation and cytotoxicity, increases cancer cell apoptosis, and may help overcome CAF‐induced immune suppression in high‐grade serous ovarian cancer. Targeting IDO1 may improve antitumor immunity.