共生微生物群通过γδT细胞促进肺癌的发展
Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.
摘要(中文译文)
肺癌与慢性炎症密切相关，但炎症的原因和特异性免疫介质尚未完全阐明。肺是一种由多种细菌群落定植的粘膜组织，肺癌患者常见的肺部感染与临床结果有关。在这里，我们提供了证据，表明局部微生物群通过激活肺部驻留的γδT细胞引发与肺腺癌相关的炎症。无菌或抗生素治疗的小鼠受到显著保护，免受Kras突变和p53缺失诱导的肺癌发展。从机制上讲，共生细菌刺激骨髓细胞产生依赖于Myd88的IL-1β和IL-23，诱导Vγ6Vδ1γδT细胞增殖和激活，产生IL-17和其他效应分子，促进炎症和肿瘤细胞增殖。我们的发现清楚地将局部微生物群-免疫串扰与肺肿瘤发展联系起来，从而确定了可能作为肺癌干预有效靶点的关键细胞和分子介质。
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 Vγ6Vδ1 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.
如何引用
AMA
Chengcheng Jin, Georgia K Lagoudas, Chen Zhao, Susan Bullman, Arjun Bhutkar, Bo Hu, et al. Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.. Cell. 2019; doi:10.1016/j.cell.2018.12.040.
APA
Chengcheng Jin, Georgia K Lagoudas, Chen Zhao, Susan Bullman, Arjun Bhutkar, Bo Hu, et al (2019). Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.. Cell. https://doi.org/10.1016/j.cell.2018.12.040
GB/T 7714
Chengcheng Jin, Georgia K Lagoudas, Chen Zhao, Susan Bullman, Arjun Bhutkar, Bo Hu, et al. Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.[J]. Cell, 2019 doi:10.1016/j.cell.2018.12.040.
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