Microbiota Modulate Tumoral Immune Surveillance in Lung through a γδT17 Immune Cell-Dependent Mechanism
Microbiota Modulate Tumoral Immune Surveillance in Lung through a γδT17 Immune Cell-Dependent Mechanism
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DOI：
10.1158/0008-5472.can-13-2462
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发表时间：
2014-08-01
期刊：
影响因子：
11.2
通讯作者：
Hu, Shilian
中科院分区：
文献类型：
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作者：
Cheng, Min;Qian, Liting;Hu, Shilian
共生菌对维持粘膜组织的免疫稳态至关重要，其生态的紊乱会影响疾病的易感性。在这里，我们报告的证据表明，肠道细菌形状的粘膜组织中的免疫监视的效率。抗生素治疗（Abt）小鼠更容易发生移植的B16/F10黑色素瘤和刘易斯肺癌，表现出平均生存时间缩短，肺部肿瘤灶更多且更大。Abt小鼠有缺陷的抗肿瘤反应与抗生素引起的脱水无关。宿主的防御依赖于没有类别特异性的完整的肠道细菌。机制研究揭示了Abt小鼠肺中γ δ T17细胞应答的诱导缺陷;在这里，观察到更具侵袭性的肿瘤发展，可能与那里IL 6和IL 23表达的减少有关。添加正常的γ δ T细胞或补充IL 17恢复了Abt小鼠中受损的免疫监视表型。总的来说，我们的研究结果证明了肠道细菌在支持宿主对癌症的免疫应答中的重要性，确定了γ δ T17应答在机制中的重要作用，并表明抗生素治疗对癌症易感性和进展的有害影响。（C）2014年AACR。
Commensal bacteria are crucial to maintain immune homeostasis in mucosal tissues and disturbances in their ecology can affect disease susceptibility. Here, we report evidence that commensal bacteria shape the efficiency of immune surveillance in mucosal tissues. Antibiotic-treated (Abt) mice were more susceptible to development of engrafted B16/F10 melanoma and Lewis lung carcinoma, exhibiting a shortened mean survival time with more numerous and larger tumor foci in the lungs. The defective antitumor response of Abt mice was independent of dehydration caused by antibiotics. Host defenses relied upon intact commensal bacteria with no class specificity. Mechanistic investigations revealed a defective induction of the gamma delta T17 cell response in lungs of Abt mice; here, more aggressive tumor development was observed, possibly related to a reduction in IL6 and IL23 expression there. Adding normal gamma delta T cells or supplementing IL17 restored the impaired immune surveillance phenotype in Abt mice. Overall, our results demonstrated the importance of commensal bacteria in supporting the host immune response against cancer, defined an important role for gamma delta T17 responses in the mechanism, and suggested deleterious effects of antibiotic treatment on cancer susceptibility and progression. (C)2014 AACR.