Figure 1.

Immunomodulatory effects of radiotherapy. Local radiation to the tumor can elicit immunogenic cell death, leading to the release of cytokines and DAMPs that in turn trigger innate signaling pathways. These signals favor the recruitment of APCs such as DCs, promote uptake of dying tumor cells, and enhance the processing of TAAs and cross-presentation of antigenic-peptides, via MHC I, to CD8⁺ T cells. Cross-presentation of tumor-antigens can lead to the priming of tumor-specific T lymphocytes, which can then traffic back to the tumor site, infiltrate into the tumor, and potentially exert cytolytic effector activity. Radiation can also induce the release of type-I IFN from both cancer and immune cells, as well as trigger complement activation, which can reinforce both DC and T cell activation. RT can also cause upregulation of MHC I, the adhesion molecule, ICAM, and the membrane protein NKG2D type II (ligand), that ultimately enhance tumor recognition and killing by T cells and NK cells, respectively. Abbreviations. DAMPs: damage associated molecular patterns; APCs: antigen presenting cells; DCs: dendritic cells; TAAs: tumor-associated antigens; MHC I: major histocompatibility complex class I; IFN: interferon; NKG2D: natural killer group 2D; NKs: natural killer cells. Figure created with the aid of biorender.com and https://smart.servier.com/.