Commensal Microbiota Promote Lung Cancer Development via γδ T Cells
Author(s)Jin, Chengcheng; Lagoudas, Georgia K; Bhutkar, Arjun; Ameh, Samuel; Sandel, Demi A; Liang, Xu Sue; Whary, Mark T.; Blainey, Paul C; Fox, James G; Jacks, Tyler E; ... Show more Show less
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Lung cancer is closely associated with chronic inflammation, but the causes of inflammation and the specific immune mediators have not been fully elucidated. The lung is a mucosal tissue colonized by a diverse bacterial community, and pulmonary infections commonly present in lung cancer patients are linked to clinical outcomes. Here, we provide evidence that local microbiota provoke inflammation associated with lung adenocarcinoma by activating lung-resident γδ T cells. Germ-free or antibiotic-treated mice were significantly protected from lung cancer development induced by Kras mutation and p53 loss. Mechanistically, commensal bacteria stimulated Myd88-dependent IL-1β and IL-23 production from myeloid cells, inducing proliferation and activation of Vγ6 + Vδ1 + γδ T cells that produced IL-17 and other effector molecules to promote inflammation and tumor cell proliferation. Our findings clearly link local microbiota-immune crosstalk to lung tumor development and thereby define key cellular and molecular mediators that may serve as effective targets in lung cancer intervention. Lung cancer development is associated with increased bacterial burden and altered bacterial composition in the lung. Depletion of microbiota or blockade of the downstream cellular or molecular immune mediators significantly suppress lung tumor growth.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Division of Comparative Medicine; Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MIT
Jin, Chengcheng et al. “Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.” Cell 176 (2019): 998-1013 © 2019 The Author(s)
Author's final manuscript