The Effects of Epigenetic Modifiers on PD‐L1 and HLA Class I Expression on Tumor Cells

Abstract

Expression of PD‐L1 on various tumor cell lines leads to the inhibition of T cell cytotoxicity. When this takes place, the T cells are unable to combat the tumor cells and cancer persists. In the same regard, increased expression of human leukocyte antigen (HLA) allows tumor cells to be more easily detected by these T cells. In previous research, epigenetic modifiers including the DNA methylation inhibitor 5‐Azacytidine (5‐AzaC) and the histone deacetylase inhibitor vorinostat, were shown to increase HLA expression. However, epigenetic modifiers have also been shown by others to upregulate PD‐L1 expression. We hope to elucidate whether or not PD‐L1 expression is upregulated along with HLA expression upon exposure to these epigenetic modifiers. If this were to occur, then the effects of both PD‐L1 and HLA would essentially negate each other. Two cell lines that are known to express PD‐L1 are MCF‐7 and MDA‐MB‐231. Our initial results confirm that PD‐L1 is expressed on the MDA‐MB‐231 cell lines, as demonstrated by flow cytometry. Our results have also shown that two other cell lines, MDA‐MB‐435 and HL‐60, do not express PD‐L1 and that exposure with the epigenetic modifier 5‐AzaC did not cause either cell line to express PD‐L1. Nonetheless, there was still an up regulation of MHC Class I antigens following a 48 hour exposure to a non‐cytotoxic dose of 5‐AzaC. Future experiments are planned to optimize the doses of 5‐AzaC and vorinostat to maximize HLA expression while not increasing or inducing the expression of PD‐L1.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.