147— The Effect of a Histone Deacetylase Inhibitor on PD-L1, HLA-ABC, HLA-E, and HLA-G on Human Breast Cancer Cell Lines

Increased expression of human leukocyte antigen (HLA) allows tumor cells to be more easily detected by the immune system. In previous research, epigenetic modifiers including the histone deacetylase inhibitor 3 (HDAC3), RGFP966, has been shown to decrease PD-L1 expression. PD-L1 expression inhibits T cell cytotoxicity, and decreasing it can enhance the immune response. We hope to elucidate whether or not HLA-ABC expression similarly decreases upon exposure to the HDAC3 inhibitor which would be detrimental to immune detection. Two breast cancer cell lines that express HLA-ABC are MCF-7 and MDA-MB-231. Our initial results show that HLA-ABC is expressed on the MDA-MB-231 and MCF-7 cell lines, while PD-L1 is only expressed by MDA-MB-231 cell line as demonstrated by flow cytometry. However, in subsequent experiments testing the effect of RGFP966, there were inconsistent results regarding the change in expression of HLA-ABC which requires further investigation. In addition, we also wish to examine other HLA proteins, such as HLA-E and HLA-G, which have been shown to be detrimental to immune detection. Future experiments are planned to optimize the doses of RGFP966 to maximize HLA expression in these breast cancer cell lines while limiting the expression of PD-L1, HLA-E and HLA-G.