期刊
CELL
卷 176, 期 5, 页码 998-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2018.12.040
关键词
-
资金
- Helen Hay Whitney Foundation-Merck postdoctoral fellowship
- Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award
- National Cancer Institute (NCI) [CA226400]
- Broad's Next10 Award
- Hugh Hampton Young Fellowship
- NCI [CA229984]
- Department of Defense [W81XWH-15-1-0623]
- Cancer Center Support (core) grant from NCI [P30-CA14051]
- Howard Hughes Medical Institute
- Broad Institute
- Career Award at the Scientific Interface from the Burroughs Wellcome Fund
- NHLBI
- NIAID, NIH
- R01 grant [CA185020]
- [P30-ES002109]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI000545] Funding Source: NIH RePORTER
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 gamma delta 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-1 beta and IL-23 production from myeloid cells, inducing proliferation and activation of V gamma 6(+)V delta 1(+) gamma delta 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据