Interferon Induces Expression of the Immune Checkpoint PD‐L1 via Bcl3 Upregulation in Ovarian Cancer Cells

Abstract

Interferon‐g (IFN) induces PD‐L1 expression in ovarian cancer (OC) cells, thus promoting OC growth. In addition to inhibiting anti‐tumor T responses, the tumor‐expressed PD‐L1 has tumor‐intrinsic effects that include increased cancer cell survival and proliferation. However, the mechanisms by which IFN induces PD‐L1 expression in OC cells are unknown. Here, we show that IFN increases gene and protein levels of the proto‐oncogene Bcl3 in ovarian cancer SKOV3 and OVCAR3 cells, resulting in their increased survival, proliferation, and migration. The IFN‐induced Bcl3 expression then promotes IFN‐mediated PD‐L1 transcription in OC cells. The mechanism consists of an IFN‐induced, Bcl3‐ and p300‐dependent PD‐L1 promoter occupancy by K314/315 acetylated p65 NFkB. Since blocking PD‐L1 by neutralizing antibody reduces proliferation of OC cells overexpressing Bcl3, these results indicate that the pro‐proliferative effect of Bcl3 in OC cells is mediated by PD‐L1. Together, our work demonstrates that IFN induces Bcl3 expression in OC cells, identifies PD‐L1 as a novel target of Bcl3, and links Bcl3 to IFN signaling and PD‐L1‐mediated immune escape.Support or Funding InformationSponsor: Dr. Ivana Vancurova (ASBMB member ID: 32743).Funding: NIH CA202775 grant (to Dr. Ivana Vancurova)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.