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Here, tumour cell death occurs when a threshold number of radiation\u2010induced non\u2010reparable double\u2010stranded DNA breaks is exceeded. However, in recent years, the importance of immune mechanisms of cell death has been increasingly recognised, as well as the impact of radiotherapy on non\u2010malignant cellular components of the tumour microenvironment. Conserved antiviral pathways that detect foreign nucleic acid in the cytosol and drive downstream interferon (IFN) responses via the cyclic guanosine monophosphate\u2013adenosine monophosphate synthase\/stimulator of IFN genes (cGAS\/STING) pathway are key components of the immune response to radiation\u2010induced DNA damage. In preclinical models, acute induction of a type 1 IFN response is important for both direct and abscopal tumour responses to radiation. Inhibitors of the DNA damage response show promise in augmenting this inflammatory IFN response. However, a substantial proportion of tumours show chronic IFN signalling prior to radiotherapy, which paradoxically drives immunosuppression. This chronic IFN signalling leads to treatment resistance, and heterotypic interactions between stromal fibroblasts and tumour cells contribute to an aggressive tumour phenotype. The effect of radiotherapy on myeloid cell populations, particularly tumour\u2010associated macrophages, has an additional impact on the immune tumour microenvironment. It is not yet clear how the above preclinical findings translate into a human context. Human tumours show greater intratumoural genomic heterogeneity and more variable levels of chromosomal instability than experimental murine models. High\u2010quality translational studies of immunological changes occurring during radiotherapy that incorporate intrinsic tumour biology will enable a better understanding of the immunological consequences of radiation\u2010induced DNA damage in patients. Copyright \u00a9 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5232","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T04:59:15Z","timestamp":1547182755000},"page":"606-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["The immunological consequences of radiation\u2010induced DNA damage"],"prefix":"10.1002","volume":"247","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0425-584X","authenticated-orcid":false,"given":"Anna C","family":"Wilkins","sequence":"first","affiliation":[{"name":"Department of Radiotherapy, The Royal Marsden NHS Foundation Trust  London UK"},{"name":"Division of Radiotherapy and Imaging The Institute of Cancer Research  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel C","family":"Patin","sequence":"additional","affiliation":[{"name":"Division of Radiotherapy and Imaging The Institute of Cancer Research  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