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However, the radioresistance of some tumour entities such as malignant melanoma limits its clinical application. The innate immune sensing receptor retinoic acid-inducible gene I (RIG-I) is ubiquitously expressed and upon activation triggers an immunogenic form of cell death in a variety of tumour cell types including melanoma. To date, the potential of RIG-I ligands to overcome radioresistance of tumour cells has not been investigated. Here, we demonstrate that RIG-I activation enhanced the extent and immunogenicity of irradiation-induced tumour cell death in human and murine melanoma cells in vitro and improved survival in the murine B16 melanoma model in\u00a0vivo. Transcriptome analysis pointed to a central role for p53, which was confirmed using p53\u2013\/\u2013 B16 cells. In vivo, the additional effect of RIG-I in combination with irradiation on tumour growth was absent in mice carrying p53\u2013\/\u2013 B16 tumours, while the antitumoural response to RIG-I stimulation alone was maintained. Our results identify p53 as a pivotal checkpoint that is triggered by RIG-I resulting in enhanced irradiation-induced tumour cell death. Thus, the combined administration of RIG-I ligands and radiotherapy is a promising approach to treating radioresistant tumours with a functional p53 pathway, such as melanoma.<\/jats:p>","DOI":"10.1093\/jmcb\/mjad001","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T15:26:51Z","timestamp":1673278011000},"source":"Crossref","is-referenced-by-count":16,"title":["RIG-I immunotherapy overcomes radioresistance in p53-positive malignant melanoma"],"prefix":"10.1093","volume":"15","author":[{"given":"Silke","family":"Lambing","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Pan","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraskevi","family":"Vasileiadou","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Holdenrieder","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"},{"name":"Institute of Laboratory Medicine, German Heart Centre , Munich 80636 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hagen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Garbe","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayk","family":"Behrendt","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schlee","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper G","family":"van den Boorn","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0556-1950","authenticated-orcid":false,"given":"Eva","family":"Bartok","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"},{"name":"Unit of Experimental Immunology, Department of Biomedical Sciences, Institute of Tropical Medicine , Antwerp 2000 , Belgium"},{"name":"Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0120-4035","authenticated-orcid":false,"given":"Marcel","family":"Renn","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"},{"name":"Mildred Scheel School of Oncology, Bonn, University Hospital Bonn, Medical Faculty , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunther","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn 53127 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"2023081110294723000_bib1","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/nm1622","article-title":"Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy","volume":"13","author":"Apetoh","year":"2007","journal-title":"Nat. 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