ABSTRACT
Several preclinical data have suggested the ability of radiation therapy to modulate the intrinsic immunogenicity of cancer cells and the tumor microenvironment, with the aim of increasing responses to checkpoint inhibitors. Early results showing a restoration of checkpoint inhibitors response in patients following irradiation have generated a lot of enthusiasm around radiation therapy beyond its usual role in local disease control. Prospective clinical trials evaluating immunoradiotherapy combinations have provided proof-of-concept that radiation therapy may induce tumor-specific T immune responses in patients treated with checkpoint inhibitors. However, these results are not always reproducible, reflecting the existence of factors related to either radiation therapy, immunotherapy and/or the host, which influence the efficacy of these combinations. Anticancer chemotherapy can play a role in amplifying the immune-radiation response by promoting tumor immunogenicity and modulating the tumor microenvironment.