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辐射诱导的双调蛋白驱动肿瘤转移。

Radiation-induced amphiregulin drives tumour metastasis.

作者信息

Piffkó András, 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

机构信息

Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA.

The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.

出版信息

Nature. 2025 May 14. doi: 10.1038/s41586-025-08994-0.

Abstract

The anti-tumour effect of radiotherapy beyond the treatment field-the abscopal effect-has garnered much interest. 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.

摘要

放射治疗在治疗区域之外的抗肿瘤作用——远隔效应——已引起广泛关注。然而,辐射在促进转移方面的潜在有害作用研究较少。在此,我们表明放射治疗可诱导肿瘤细胞中表皮生长因子受体(EGFR)配体双调蛋白的表达,这会使表达EGFR的髓样细胞重编程为免疫抑制表型并减少吞噬作用。这会促进人类患者和临床前小鼠肿瘤模型中的远处转移生长。抑制放射治疗诱导的这些促肿瘤因子可能代表一种改善患者预后的新治疗策略。

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