Fig. 4
From: Epigenetic remodeling of the immune landscape in cancer: therapeutic hurdles and opportunities
Therapeutic effects of DNMT inhibitors on different types of immune cells in the tumor immune microenvironment. DNA methyltransferase inhibitors (DNMTis) possess both anti-tumor and pro-tumor effects via reprogramming different immune cell types in TIME. DNMTi treatment of cancer cells exerts anti-tumor memory effects, induces anti-viral interferon responses, promote expression of tumor-associated antigens, as well as upregulation of antigen processing and presentation machineries, which enhances the recognition and lysis of cancer cells by effector T cells. Besides, DNMTi appears to reinvigorate dysfunctional T cells and shift the exhaustion state towards an effector T cell phenotype. Furthermore, DNMTi significantly promotes immune synapse formation and cytoskeletal reorganization, leading to robust cancer killing by cytotoxic γδ T cells. Besides, DNMTi promotes anti-tumor immunity by reducing myeloid-derived suppressor cells (MDSC) and disrupting premetastatic niches established by MDSC. Interestingly, DNMTis show bifacial effects on natural killer (NK) cells and may either suppress NK cell-mediated cancer killing or boost NK cell-mediated recognition of cancer cells. On the other hand, DNMTi may exert pro-tumor effects by promoting lineage development and suppressive function of Treg. This figure was created on BioRender.com