Histone post-translational modifications and DNA methylation play key roles in adaptive immune response, including dendritic cell development and T cell priming and activation. In tumor cells, histone and DNA modifications affects production of tumor antigens, silencing of anti-tumor cytokines, and induction of the PD-L1 checkpoint. Recent studies revealed the contributions of chromatin remodeling responding to cytotoxic attack in tumor cells and exhaustion phenotype in tumor infiltrating CD8 T cells. Abbreviation: PD-L1, programmed death ligand 1.