Interferon‐γ Induces PD‐L1 Expression in Ovarian Cancer Cells by JAK/STAT1 Signaling

Abstract

Interferon‐γ (IFNγ) is a pleiotropic cytokine critical for immune functions and tumor immunity. Although IFNγ has been used in the treatment of different types of cancer, including ovarian cancer (OC), most clinical trials using IFNγ to treat solid tumors have produced mixed or disappointing results. Recent studies have shown that IFNγ induces expression of the immune checkpoint PD‐L1 in OC cells, resulting in their increased proliferation and tumor growth. However, the mechanisms that regulate the PD‐L1 expression in OC remain poorly understood. Since one of the main pathways induced by IFNγ is the JAK/STAT pathway, we investigated whether the IFNγ‐induced PD‐L1 expression in OC cells is regulated by JAK/STAT signaling. Here, we show that IFNγ induces STAT1 expression and STAT1 phosphorylation on Tyr‐701 and Ser‐727 in OC cells. In addition, JAK1 suppression significantly decreases the IFNγ‐induced PD‐L1 mRNA and protein levels in OC cells, demonstrating that the IFNγ‐induced PD‐L1 expression in OC cells is dependent on JAK1 activity. Together, our results indicate that the IFNγ‐induced PD‐L1 expression in OC cells is regulated by JAK/STAT1 signaling. Understanding the mechanisms of how IFNγ induces the PD‐L1 expression in OC cells will contribute to the development of therapeutic strategies aimed to increase the anti‐tumor effects of IFNγ, and modulate the levels of PD‐L1 in ovarian cancer.Support or Funding InformationNIH CA202775 grant