Open AccessRadiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
Author(s) -
Emma Nolan,
Victoria L. Bridgeman,
Luigi Ombrato,
Adam Karoutas,
Nicolas Rabas,
Celine Angeli Natascha Sewneth,
Marcos Vásquez,
Felipe Silva Rodrigues,
Stuart Horswell,
Peter Faull,
Rebecca Carter,
Ilaria Malanchi
Publication year - 2022
Publication title -
nature cancer
Language(s) - English
Resource type - Journals
ISSN - 2662-1347
DOI - 10.1038/s43018-022-00336-7
Subject(s) - lung cancer , cancer research , metastasis , medicine , cancer , radiation therapy , lung , tumor microenvironment , context (archaeology) , pathology , biology , paleontology
Radiotherapy is one of the most effective approaches to achieve tumor control in cancer patients, although healthy tissue injury due to off-target radiation exposure can occur. In this study, we used a model of acute radiation injury to the lung, in the context of cancer metastasis, to understand the biological link between tissue damage and cancer progression. We exposed healthy mouse lung tissue to radiation before the induction of metastasis and observed a strong enhancement of cancer cell growth. We found that locally activated neutrophils were key drivers of the tumor-supportive preconditioning of the lung microenvironment, governed by enhanced regenerative Notch signaling. Importantly, these tissue perturbations endowed arriving cancer cells with an augmented stemness phenotype. By preventing neutrophil-dependent Notch activation, via blocking degranulation, we were able to significantly offset the radiation-enhanced metastases. This work highlights a pro-tumorigenic activity of neutrophils, which is likely linked to their tissue regenerative functions.