Epigenetic silencing including histone modifications and DNA methylation is an important tumorigenic mechanism 1 However, its role in cancer immunopathology and immunotherapy is poorly understood. Using ovarian cancers as our model, we found that enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27me3) and DNA methyltransferase (DNMT) 1-mediated DNA methylation repress the tumor production of Th1-type chemokines CXCL9 and CXCL10, and subsequently determine effector T cell trafficking to the tumor microenvironment. Treatment with epigenetic modulators removes the repression and increases effector T cell tumor infiltration, slows down tumor progression, and improves therapeutic efficacy of PD-L1 (B7-H1) checkpoint blockade 2– 4 and adoptive T cell transfusion 5 in tumor bearing mice. Moreover, tumor EZH2 and DNMT1 are negatively associated with tumor infiltrating CD8 + T cells and patient outcome. Thus, epigenetic silencing of Th1-type chemokine is a novel tumor immune evasion mechanism. Selective epigenetic reprogramming alters T cell landscape 6 in cancer and may enhance clinical efficacy of cancer therapy.