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Senescent alveolar macrophages promote early-stage lung tumorigenesis. | LitMetric

Senescent alveolar macrophages promote early-stage lung tumorigenesis.

Cancer Cell

Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA; Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA; Paul F. Glenn Center for Biology of Aging Research at Mayo Clinic, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA; The Robert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. Electronic address:

Published: July 2023

AI Article Synopsis

Article Abstract

Senescent cells play relevant but context-dependent roles during tumorigenesis. Here, in an oncogenic Kras-driven lung cancer mouse model, we found that senescent cells, specifically alveolar macrophages, accumulate early in neoplasia. These macrophages have upregulated expression of p16 and Cxcr1, are distinct from previously defined subsets and are sensitive to senolytic interventions, and suppress cytotoxic T cell responses. Their removal attenuates adenoma development and progression in mice, indicating their tumorigenesis-promoting role. Importantly, we found that alveolar macrophages with these properties increase with normal aging in mouse lung and in human lung adenocarcinoma in situ. Collectively, our study indicates that a subset of tissue-resident macrophages can support neoplastic transformation through altering their local microenvironment, suggesting that therapeutic interventions targeting senescent macrophages may attenuate lung cancer progression during early stages of disease.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10524974PMC
http://dx.doi.org/10.1016/j.ccell.2023.05.006DOI Listing

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