CTLA4 and neoplasm: Additionally, this mechanism regulates immune tolerance within the TME.236 The upregulation of Ezh2 expression in the tumor has been demonstrated in three distinct melanoma mouse models (B16-F10, RIM3, and NrasQ61KInk4a−/−) following anti-CTLA-4 antibody therapy.237 The upregulation leads to the epigenetic silencing of immune-related genes in tumors, such as Cxcl9, in contrast to the control group.