<p>The anti-tumour effect of radiotherapy beyond the treatment field—the abscopal effect—has garnered much interest<sup><CitationRef CitationID="CR1">1</CitationRef></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>

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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,
  • Ralph R. Weichselbaum

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.