Radiation-induced amphiregulin drives tumour metastasis

• 成果类型: Article
• 署名作者: Piffko, Andras; Yang, Kaiting; Panda, Arpit; Heide, Janna; Tesak, Krystyna; Wen, Chuangyu; Zawieracz, Katarzyna; Wang, Liangliang; Naccasha, Emile Z.; Bugno, Jason; Fu, Yanbin; Chen, Dapeng; Donle, Leonhard; Lengyel, Ernst; Tilley, Douglas G.; Mack, Matthias; Rock, Ronald S.; Chmura, Steven J.; Vokes, Everett E.; He, Chuan; Pitroda, Sean P.; Liang, Hua Laura; Weichselbaum, Ralph R.
• 署名单位: University of Chicago; University of Chicago; University of Hamburg; University Medical Center Hamburg-Eppendorf; South China University of Technology; University of Chicago; University of Chicago; University of Chicago; Howard Hughes Medical Institute; University of Chicago; University of Chicago; Chinese Academy of Sciences; Institute of Microbiology, CAS; University of Chicago; Cornell University; Weill Cornell Medicine; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University; University of Regensburg; University of Chicago
• 刊物名称: Nature
• ISSN/ISSBN: 0028-1604
• DOI: 10.1038/s41586-025-08994-0
• 发表日期: 2025-07-17
• 关键词: growth-factor-receptor; cell lung-cancer; stereotactic body radiotherapy; single-cell; t-cells; gene-expression; macrophages; gefitinib; egfr; chemoradiotherapy

摘要

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.