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Radiation-induced amphiregulin drives tumour metastasis

Author

Listed:
  • András Piffkó

    (University of Chicago
    University of Chicago
    University Medical Center Hamburg-Eppendorf)

  • Kaiting Yang

    (University of Chicago
    University of Chicago
    Guangzhou International Campus)

  • Arpit Panda

    (University of Chicago
    University of Chicago)

  • Janna Heide

    (University of Chicago)

  • Krystyna Tesak

    (University of Chicago
    University of Chicago
    University of Chicago)

  • Chuangyu Wen

    (University of Chicago
    University of Chicago)

  • Katarzyna Zawieracz

    (University of Chicago)

  • Liangliang Wang

    (University of Chicago
    University of Chicago
    Chinese Academy of Sciences)

  • Emile Z. Naccasha

    (University of Chicago
    University of Chicago)

  • Jason Bugno

    (University of Chicago
    University of Chicago
    University of Chicago)

  • Yanbin Fu

    (University of Chicago
    University of Chicago
    Weill Cornell Medicine)

  • Dapeng Chen

    (University of Chicago
    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
    University of Chicago)

  • Everett E. Vokes

    (University of Chicago)

  • Chuan He

    (University of Chicago
    University of Chicago)

  • Sean P. Pitroda

    (University of Chicago
    University of Chicago)

  • Hua Laura Liang

    (University of Chicago
    University of Chicago)

  • Ralph R. Weichselbaum

    (University of Chicago
    University of Chicago)

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.

Suggested Citation

  • 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 , 2025. "Radiation-induced amphiregulin drives tumour metastasis," Nature, Nature, vol. 643(8072), pages 810-819, July.
    • Handle: RePEc:nat:nature:v:643:y:2025:i:8072:d:10.1038_s41586-025-08994-0
    DOI: 10.1038/s41586-025-08994-0
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