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The Effect of a Histone Deacetylase Inhibitor on PD‐L1, HLA‐ABC, HLA‐E, and HLA‐G on Human Breast Cancer Cell Lines
Author(s) -
Toufexis Alec George,
Reddy Nikhil Cheruku,
O’Donnell Robert W.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06078
Subject(s) - histone deacetylase inhibitor , human leukocyte antigen , immune system , hla g , immunosurveillance , cancer research , histone deacetylase , cancer , flow cytometry , cancer cell , cell culture , biology , immunology , antigen , histone , genetics , gene
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 leads to inhibition of T cell cytotoxicity, and decreasing it therefore can enhance the immune response. We hope to elucidate whether or not HLA‐ABC expression is similarly decreased upon exposure to the HDAC3 inhibitor which would be detrimental to immune detection. Two breast cancer cell lines that are known to 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 the drug RGFP966, there were inconsistent results regarding the change in expression of HLA‐ABC which requires further investigation. In addition, we also wish to look at other HLA proteins, such as HLA‐E and HLA‐G, of which expression which has 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 and HLA‐E and HLA‐G. Support or Funding Information Geneseo Foundation Carl Savino ‘53 and Olga Gerych‐Savino ‘53 Endowment David Wolf, DO