Immune modulatory functions of EZH2 in the tumor microenvironment: implications in cancer immunotherapy

Polycomb group protein EZH2, a histone methyltransferase, is the enzymatic subunit of the Polycomb Repressive Complex 2 (PRC2) that catalyzes histone H3 lysine 27 methylation. They are epigenetic modifiers that mediate gene repression, or epigenetic silencing. EZH2 controls developmental regulators in embryonic stem cells and is essential for cell fate determination and transition. In the last two decades, EZH2 was reported upregulated in a variety of solid tumors, including prostate cancer, and mutated in multiple hematological malignancies, such as lymphoma. EZH2 represses the expression of a plethora of tumor suppressor genes in tumor cells, thereby promoting cell cycle, cell proliferation, and cell invasion and driving cancer progression. Recently, evidence is emerging indicating important roles of EZH2 in immune cells. Here, we review EZH2 regulation of various immune cell types, the tumor microenvironment, immune responses, and cancer immunotherapies.