Concomitant Mycobacterium tuberculosis infection promotes lung tumor growth through enhancing Treg development.
Concomitant Mycobacterium tuberculosis infection promotes lung tumor growth through enhancing Treg development.
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伴随结核分枝杆菌感染通过增强 Treg 发育促进肺肿瘤生长
DOI：
10.3892/or.2017.5733
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发表时间：
2017-08
期刊：
影响因子：
4.2
通讯作者：
Zhong H
中科院分区：
文献类型：
--
作者：
Zhou Y;Hu Z;Cao S;Yan B;Qian J;Zhong H
肺癌是人类最常见的恶性肿瘤。肿瘤相关微环境中CD 4 + Foxp 3+调节性T细胞（TCRs）数量的增加在癌症免疫逃避中起着重要作用。H37 Rv在非小细胞肺癌（NSCLC）发生发展中的确切作用及其机制尚不清楚。在这里，我们发现H37 Rv感染促进NSCLC细胞生长，在引流淋巴结中发现更高百分比的TcB。我们还在体外确定了H37 Rv感染诱导巨噬细胞成熟和PD-L1表达，这促进了Treg比例，具有增强的增殖抑制功能。机制分析显示AKT-mTORC 1信号在H37 Rv感染诱导PD-L1表达中起重要作用。通过雷帕霉素或raptor缺陷抑制AKT-mTORC 1信号显示PD-L1水平降低，这进一步降低了共培养系统中Treg的比例。最后，与单独注射H37 Rv相比，注射H37 Rv加雷帕霉素的荷瘤小鼠增强了肺癌的免疫应答。本研究证明H37 Rv合并感染通过提高Treg比例促进NSCLC肿瘤免疫应答。
Lung cancer is the most common malignancy in humans. An increased population of CD4+Foxp3+ regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. The exact role and the involved mechanisms of concomitant H37Rv infection in non-small cell lung cancer (NSCLC) development are still not clear. Here, we showed that H37Rv infection promoted NSCLC cell growth with a higher percentage of Tregs found in draining lymph nodes. We also determined in vitro that H37Rv infection induced macrophage maturation and PD-L1 expression, which promoted Treg proportion, with enhanced proliferation suppression function. Mechanism analysis revealed that AKT-mTORC1 signal was important for PD-L1 expression induced by H37Rv infection. Suppressing of AKT-mTORC1 signal by rapamycin or raptor deficiency showed decreased PD-L1 levels which further reduced Treg proportion in a co-culture system. Finally, tumor-bearing mice injected with H37Rv plus rapamycin enhance the immune response of lung cancer compared with injected with H37Rv alone. This study demonstrated that concomitant H37Rv infection promote NSCLC tumor immune eacape through enhancing Treg proportion.
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影响因子：
4.5
作者：
Kim JO;Jung SS;Kim SY;Kim TY;Shin DW;Lee JH;Lee YH
通讯作者：
Lee YH
影响因子：
5.4
作者：
Garg, Ankita;Barnes, Peter F.;Vankayalapati, Ramakrishna
通讯作者：
Vankayalapati, Ramakrishna
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH
DOI：
10.1007/s10096-010-0908-0
发表时间：
2010-06-01
影响因子：
4.5
作者：
He, X-Y;Xiao, L.;Shi, B-Y
通讯作者：
Shi, B-Y
全反式视黄酸在 TGF-β 介导的 Foxp3 和 Il10 基因在发育调节性 T 细胞中的诱导中的对比作用。
DOI：
10.1084/jem.20080950
发表时间：
2009-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Maynard CL;Hatton RD;Helms WS;Oliver JR;Stephensen CB;Weaver CT
通讯作者：
Weaver CT