Marked Global DNA Hypomethylation Is Associated with Constitutive PD-L1 Expression in Melanoma.

ABSTRACT: Constitutive expression of the immune checkpoint, PD-L1, inhibits anti-tumor immune responses in cancer, although the factors involved in PD-L1 regulation are poorly understood. Here we show that loss of global DNA methylation, particularly in intergenic regions and repeat elements, is associated with constitutive (PD-L1_CON), versus inducible (PD-L1_IND), PD-L1 expression in melanoma cell lines. We further show this is accompanied by transcriptomic up-regulation. De novo epigenetic regulators (e.g., DNMT3A) are strongly correlated with PD-L1 expression and methylome status. Accordingly, decitabine-mediated inhibition of global methylation in melanoma cells leads to increased PD-L1 expression. Moreover, viral mimicry and immune response genes are highly expressed in lym

SUBMITTER: Chatterjee A 

PROVIDER: S-EPMC6147024 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature