Upregulating Human Leukocyte Antigen Expression in Multiple Cancer Cells through Epigenetic Modulators

Abstract

This study attempts to discern whether two epigenetic modulators, 5‐Azacytidine and Entinostat, increase the expression of Human Leukocyte Antigen (HLA) proteins on human cancer cells when used in combination. HLA is routinely down‐regulated in cancer, presumably to escape immunologic detection. We have previously shown that 5‐Azacytidine, a cytosine DNA methyltransferase inhibitor, increased HLA expression. Others have shown that Entinostat, an epigenetic modulator that functions as a histone deacetylase inhibitor, can modify tumor growth both in vivo and in vitro. Five cancer cell lines, HL‐60, MDA‐MB‐435, MDA‐MB‐231, MCF‐7, and HTB‐4 cells are being tested using flow cytometry and Phycoerythrin (PE) conjugated antibodies against the HLA Class I antigens A, B and C. Initial findings show that Entinostat, and/or the combination of Entinostat and 5‐Azacytidine, are more effective at up‐regulating HLA expression than 5‐Azacytidine alone in HL‐60, HTB‐4, and MDA‐MB‐435 cell lines. Further cells lines will be tested to determine if Entinostat or the combination will be more effective in up‐regulating HLA expression as well as the optimal dose and exposure time. If 5‐Azacytidine and Entinostat are shown to work in synergy, cancer cells could become better targets for cancer immunotherapy.Support or Funding InformationGeneseo Foundation and the SUNY Geneseo Biology Department