Fig. 4

EZH2 inhibitors and tumor immune effects. The inactivation of NSD1 (the decisive H3K36me2 catalytic enzyme in embryonic stem cells) results in transcriptional suppression of innate immune genes and decreased infiltration of immune cells into tumors by deleting H3K36me2 and increasing H3K27me3. Inhibiting EZH2 can reactivate the interferon response, restore immune cell infiltration, and impede the growth of NSD1 mutant SCC [111]. EZH2 inhibitors enhance the activity of CD8 T effector cells, stimulate the secretion of chemokines by tumor-infiltrating DC cells, and facilitate the trafficking of effector T cells to the tumor microenvironment (TME). They also decrease the stability of the Treg lineage, impair its function, and partially overcome immune checkpoint inhibitor resistance. Additionally, EZH2 inhibitors promote the maturation and activation of NK cells, as well as increase the expression of activating receptors, thus bolstering innate anti-tumor immunity [112]