Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.

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PubMed ID: 30712876

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Jin C, Lagoudas GK, Zhao C, Bullman S, Bhutkar A, Hu B, Ameh S, Sandel D, Liang XS, Mazzilli S, Whary MT, Meyerson M, Germain R, Blainey PC, Fox JG, Jacks T

Cell. Feb 2019


COMMENT: The authors prove that the lung adenocarcinoma associated inflammation might be caused by the activation of lung-resident gamma delta T cells by local lung microbiome.


In the current study, we investigated the host-microbiota interaction in lung cancer development using a genetically engineered mouse (GEM) model driven by an activating point mutation of Kras and loss of p53, which are frequently associated with human LUAD (lung adenocarcinoma)


Here, we provide evidence that local microbiota provoke inflammation associated with lung adenocarcinoma by activating lung-resident gd 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-1b and IL-23 production from myeloid cells, inducing proliferation and activation of Vg6+Vd1+ gd 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


Marina Manrique