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

  • FEBS Open Bio. 2025 Oct 13. doi: 10.1002/2211-5463.70126.
Hyewon Lee  1  2 ,  Jung Yoon Ho  1  2 ,  In Sun Hwang  1 ,  Youn Jin Choi  1  2
Affiliations
  • 1. Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 2. Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
PMID: 41078340 DOI: 10.1002/2211-5463.70126
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.

Keywords
IDO1; cancer‐associated fibroblasts; immunosuppression; ovarian cancer; tumor microenvironment.
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