Landscape of immune-related signatures induced by targeting of epigenetic regulators in melanoma II. Landscape of immune-related signatures induced by targeting of epigenetic regulators in melanoma II

Epigenetic drugs exert a wide range of immune-related effects, but have strong drug-specific heterogeneity in immunomodulation, thus hampering selection of the most promising agent for innovative cancer immunotherapy approaches. Here we identified immune-related signatures induced by four classes of epigenetic drugs in melanoma cells to define the most active agent and to understand its biological activity in -vitro, in a pre-clinical model and in clinical samples. Gene modulation, induced by inhibitors of DNA methyltransferases (guadecitabine), histone deacetylases (givinostat), bromodomain and extraterminal domain proteins (JQ1 and OTX-015) and enhancer of zeste homolog 2 (GSK126), was assessed in human melanoma cell lines. All drugs modulated genes belonging to 20 families. Guadecitabine, followed by givinostat, was the most active drug and upregulated >160 immune-related genes characterized by low expression and high methylation. JQ1 and OTX-015 showed predominant inhibitory effects, GSK126 was the least active. A dominant immunomodulatory effect of guadecitabine and JQ1 was observed in combinatorial treatments. This experiment deals with the characterization of gene modulation by epigenetic drugs (guadecitabine, givinostat, JQ1, GSK-126) and by the unrelated drug Abemaciclib in two melanoma cells lines CST30 and VRG100 Overall design: Whole genome gene expression was assessed by Clariom S arrays in two cell lines CST30 and VRG100 treated or not with epigenetic drugs.