Ionizing radiation (IR) is used as primary treatment for numerous localized cancers. Although it is usually described as an immunosuppressive modality, there are new preclinical evidences suggesting that IR could have also generated substantial changes in the tumor microenvironment, including triggering an inflammatory process. This finding implies that radiotherapy could both modulate tumor immunity and have out-of-field activity by recruiting biological effectors. There are numerous uncertainties regarding the true biological impact of radiation on tumor immunogenicity, but some preclinical studies established the proof of concept that combining IR with strategies modifying immunology could enhance antitumor effects. From these findings, clinical trials are now analyzing how immunotherapy and radiation work while given together, with promising preliminary results. This review aims at summarizing the recent developments regarding the impact of IR on tumor immunity, with focus on potential therapeutic targets.
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