PD-L1 Expression Due to Epigenetic Modifications During Histone Deacetylase Inhibition in Cancer Cells

Nova Southeastern University, Davie, Florida, USA

Objective: We analyzed the expression of PD-L1 following inhibition of HDACs (Histone Deacetylase) with SAHA (Suberoylanilide Hydroxamic Acid). Background: SAHA is a broad-spectrum HDAC Inhibitor, which plays an important role in regulating the gene expressions to induce cell cycle arrest and cell death in cancer cells. Programmed Cell Death Ligand-1 (PD-L1) can be expressed on the surface of cancer cells, which typically confers aggressive growth and immune-suppression characteristics. SAHA treatment was expected to alter PD-L1 expression in cancer cells. Methods: The HCC827 cells were treated with HDACi and used for gene expression analysis using Microarray, qRT-PCR and Western blot. Results: SAHA treatment was able to reduce the levels of PD-L1 expression in a dose and time-dependent manner. The PD-L1 level was found to be negatively correlated to the p21 expression in HCC827 cells after treatment with HDACi. Interestingly the qRT-PCR Array analysis revealed significant decreases in the mRNA levels of methyltransferases such as DNMT3A, DNMT3B, PRMT1, SUV39H1, KAT6B, NSD1, SETD1B, and WHSC1. SAHA treatment increased the levels of acetyl forms of H2B, H3, and H4, while decreasing the levels of the methyltransferases. Conclusion: HDACi treatment was leading to hyper-acetylation of histones while the levels of methyltransferases were decreased significantly. It is suspected that the decrease in the PD-L1 and methyltransferases levels are due to inhibition of transcription following treatment with SAHA. Grants: Research was supported by the Royal Dames of Cancer Research Inc., Fort Lauderdale, Florida.