CTLA4 and cancer: However, anti-CTLA4, the first monoclonal antibody used in cancer therapy as an immune checkpoint, induces an upregulation of EZH2 expression191 which may prevent anti-tumor immunity by inducing an immunosuppressive tumor microenvironment.190,191 A synergistic strategy coupling anti-CTLA4 and an EZH2 inhibitor reverses cancer resistance to the immune system.191,192 Moreover, considering the involvement of PcG proteins in pluripotency, it is not surprising that PcG proteins are also involved in cancer stem cell (CSC) development and resistance to treatment.