András Piffkó, Kaiting Yang, Arpit Panda, Janna Heide, Krystyna Tesak, Chuangyu Wen, Katarzyna Zawieracz, Liangliang Wang, Emile Z. Naccasha, Jason Bugno, Yanbin Fu, Dapeng Chen, Leonhard Donle, Ernst Lengyel, Douglas G. Tilley, Matthias Mack, Ronald S. Rock, Steven J. Chmura, Everett E. Vokes, Chuan He, Sean P. Pitroda, Hua Laura Liang, Ralph R. Weichselbaum
{"title":"Radiation-induced amphiregulin drives tumour metastasis","authors":"András Piffkó, Kaiting Yang, Arpit Panda, Janna Heide, Krystyna Tesak, Chuangyu Wen, Katarzyna Zawieracz, Liangliang Wang, Emile Z. Naccasha, Jason Bugno, Yanbin Fu, Dapeng Chen, Leonhard Donle, Ernst Lengyel, Douglas G. Tilley, Matthias Mack, Ronald S. Rock, Steven J. Chmura, Everett E. Vokes, Chuan He, Sean P. Pitroda, Hua Laura Liang, Ralph R. Weichselbaum","doi":"10.1038/s41586-025-08994-0","DOIUrl":null,"url":null,"abstract":"<p>The anti-tumour effect of radiotherapy beyond the treatment field—the abscopal effect—has garnered much interest<sup>1</sup>. However, the potentially deleterious effect of radiation in promoting metastasis is less well studied. Here we show that radiotherapy induces the expression of the EGFR ligand amphiregulin in tumour cells, which reprogrammes EGFR-expressing myeloid cells toward an immunosuppressive phenotype and reduces phagocytosis. This stimulates distant metastasis growth in human patients and in pre-clinical mouse tumour models. The inhibition of these tumour-promoting factors induced by radiotherapy may represent a novel therapeutic strategy to improve patient outcomes.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"4 1","pages":""},"PeriodicalIF":50.5000,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41586-025-08994-0","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
The anti-tumour effect of radiotherapy beyond the treatment field—the abscopal effect—has garnered much interest1. However, the potentially deleterious effect of radiation in promoting metastasis is less well studied. Here we show that radiotherapy induces the expression of the EGFR ligand amphiregulin in tumour cells, which reprogrammes EGFR-expressing myeloid cells toward an immunosuppressive phenotype and reduces phagocytosis. This stimulates distant metastasis growth in human patients and in pre-clinical mouse tumour models. The inhibition of these tumour-promoting factors induced by radiotherapy may represent a novel therapeutic strategy to improve patient outcomes.
期刊介绍:
Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.