Radiation-induced amphiregulin drives tumour metastasis

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 and Ralph R. Weichselbaum ()
Additional contact information
András Piffkó: University of Chicago
Kaiting Yang: University of Chicago
Arpit Panda: University of Chicago
Janna Heide: University of Chicago
Krystyna Tesak: University of Chicago
Chuangyu Wen: University of Chicago
Katarzyna Zawieracz: University of Chicago
Liangliang Wang: University of Chicago
Emile Z. Naccasha: University of Chicago
Jason Bugno: University of Chicago
Yanbin Fu: University of Chicago
Dapeng Chen: University of Chicago
Leonhard Donle: University of Chicago
Ernst Lengyel: University of Chicago
Douglas G. Tilley: Temple University
Matthias Mack: University of Regensburg
Ronald S. Rock: University of Chicago
Steven J. Chmura: University of Chicago
Everett E. Vokes: University of Chicago
Chuan He: University of Chicago
Sean P. Pitroda: University of Chicago
Hua Laura Liang: University of Chicago
Ralph R. Weichselbaum: University of Chicago

Nature, 2025, vol. 643, issue 8072, 810-819

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41586-025-08994-0

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