Figure 3.

Synergistic effects of RT, immunotherapy and DNMTis. RT acts on cancer cells to produce double-stranded DNA, release cancer-specific peptides, and activate the cGAS-STING-IFN-I pathway to promote anti-tumor immunity. DNMTis remove methylation from endogenous retroviruses and activates type I interferon signal via TLR3 and MDA3 sensors, while releasing cancer testis antigens, which are involved in antigen processing and presentation, and anti-tumor immunity. RT and DMNTis can also promote the expression of PD-L1 in cancer cells and improve the efficacy of immunotherapy. In addition, they can also affect the TME, which is conducive to the formation of anti-tumor immune microenvironment. DNMTis make cancer cells more sensitive to RT and immunotherapy, which work in concert with each other to achieve long-lasting and effective anti-tumor effects. RT, radiotherapy; CSPs, cancer-specific peptides; ERVs, endogenous retroviruses; CTAs, cancer testis antigens; DNMTis, DNA methyltransferase inhibitors; MDSC, myeloid-derived suppressor cell; TAM, tumor-associated macrophage; cGAS, cyclic GMP-AMP synthase; STING, stimulator of interferon genes; MHC-I, major histocompatibility antigen-I; IFN-I, interferon I; IFNGR1, interferon gamma receptor 1; TCR, T cell receptor.