Figure 1.

Schematic overview illustrating the mechanisms of synergy between radiotherapy and immunotherapy. Radiation therapy induces immunomodulatory effects that can boost anti-tumor immunity in several ways. Damage and death of cancer cells by radiation causes the release of tumor associated antigens, increased calreticulin, DAMPS which activate dendritic cells which prime CD8⁺ cytotoxic T cells. The activation of the cGAS-STING Pathway further leads to increase in pro-inflammatory cytokines, especially type I interferons which help to recruit active immune cells to the tumor microenvironment. The addition of immune checkpoint inhibitors such as anti-CTLA4 and anti-PD1/PD-L1 based therapies work synergistically with radiation therapy to promote an effective anti-tumor response. An anti-tumor immune response seen at a distant non-irradiated site through the abscopal effect may be one such benefit of combining immunotherapy with radiation (Elements of diagram created with Biorender.com). GI, gastrointestinal; DAMPs, damage associated molecular patterns; cGAS-STING, cyclic GMP-AMP synthase-stimulator of interferon genes; CTLA4, cytotoxic T lymphocyte-associated antigen 4; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1.