The immune checkpoint programmed death ligand-1 (PD-L1) is highly expressed in cancer cells, including ovarian cancer (OC) cells. High PD-L1 expression in ovarian cancer correlates with poor prognosis, but the mechanisms that regulate the PD-L1 expression in OC remain poorly understood. We have recently shown that IFNγ induces the PD-L1 expression in OC cells, resulting in their increased proliferation and invasion. Here, we show that the IFNγ-induced PD-L1 expression in OC cells is associated with increased levels of STAT1, Tyr-701 pSTAT1 and Ser-727 pSTAT1 in OC cells. JAK1 and STAT1 suppression significantly decreases the IFNγ-induced PD-L1 mRNA and protein levels in OC cells. In addition, IRF1 suppression significantly decreases the IFNγ-induced gene and protein levels of PD-L1, indicating that the IFNγ-induced PD-L1 expression in OC cells is dependent on IRF1 signaling. Chromatin immunoprecipitation data demonstrate that IFNγ induces occupancy of STAT1, Ser-727 pSTAT1 and IRF1 at STAT1 and IRF1 binding sites in human PD-L1 promoter. Together, these results show that the IFNγ-induced PD-L1 expression in OC cells is regulated by IRF1/JAK1/STAT1 signaling, and suggest that targeting the IRF1/JAK1/STAT1 pathway may provide leverage to regulate the PD-L1 levels in ovarian cancer.
