dc.contributor.author | Jin, Chengcheng | |
dc.contributor.author | Lagoudas, Georgia K | |
dc.contributor.author | Bhutkar, Arjun | |
dc.contributor.author | Ameh, Samuel | |
dc.contributor.author | Sandel, Demi A | |
dc.contributor.author | Liang, Xu Sue | |
dc.contributor.author | Whary, Mark T. | |
dc.contributor.author | Blainey, Paul C | |
dc.contributor.author | Fox, James G | |
dc.contributor.author | Jacks, Tyler E | |
dc.date.accessioned | 2020-05-14T15:18:18Z | |
dc.date.available | 2020-05-14T15:18:18Z | |
dc.date.issued | 2019-02 | |
dc.identifier.issn | 0092-8674 | |
dc.identifier.uri | https://hdl.handle.net/1721.1/125235 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) ( K99 Award CA226400) | en_US |
dc.description.sponsorship | United States. Department of Defense. Lung Cancer Research Program ( Concept Award W81XWH-15–1–0623) | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) ( R01 Grant CA185020) | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) (Core Grant P30-CA14051) | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) (Grant P30-ES002109) | en_US |
dc.language.iso | en | |
dc.publisher | Elsevier BV | en_US |
dc.relation.isversionof | 10.1016/J.CELL.2018.12.040 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Commensal Microbiota Promote Lung Cancer Development via γδ T Cells | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Jin, Chengcheng et al. “Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.” Cell 176 (2019): 998-1013 © 2019 The Author(s) | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Division of Comparative Medicine | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.relation.journal | Cell | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2020-03-04T13:46:50Z | |
dspace.date.submission | 2020-03-04T13:46:52Z | |
mit.journal.volume | 176 | en_US |
mit.journal.issue | 5 | en_US |
mit.license | PUBLISHER_CC | |
mit.metadata.status | Complete | |