Mycobacterium tuberculosis antigens repress Th1 immune response suppression and promotes lung cancer metastasis through PD-1/PDI-1 signaling pathway
Mycobacterium tuberculosis antigens repress Th1 immune response suppression and promotes lung cancer metastasis through PD-1/PDI-1 signaling pathway
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DOI：
10.1038/s41419-018-1237-y
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发表时间：
2019-01-18
影响因子：
9
通讯作者：
Zhong, Hua
中科院分区：
文献类型：
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作者：
Cao, Shuhui;Li, Jingwen;Zhong, Hua
鉴于世界上三分之一的人口感染了结核分枝杆菌(MTB)，确定结核病和肺癌之间的潜在分子机制是很重要的。本研究通过T细胞介导的免疫应答，探讨结核分枝杆菌感染对肺癌细胞肺转移的免疫应答。为了阐明这一问题，我们分析了MTB患者的抗原特异性T细胞和野生型和PD-1基因敲除小鼠脾淋巴细胞在MTB抗原刺激和Lewis肺癌细胞注射后的PD-1、PD-L1和PD-L2的表达水平和免疫功能。我们的数据表明，活动性肺结核患者以及接受MTB和肺癌细胞治疗的小鼠的PD-1、PD-L1和PD-L2的表达水平都升高。我们还观察到MTB抑制T细胞介导的细胞免疫反应，而MTB则显着促进肺内肿瘤的转移。综上所述，PD-1/PD-L途径是MTB抑制T细胞免疫应答、促进肿瘤转移所必需的。本研究提供的证据表明，阻断PD-1/PD-L1信号通路可能有利于结核分枝杆菌或其他慢性感染患者，甚至阻止他们的癌症发展。
Given one-third of the world's population is infected with Mycobacterium tuberculosis (MTB), it is important to identify the underling molecular mechanism between development of TB and lung cancer. This study investigated the immune response to MTB infection on lung metastasis in lung cancer cells via T cell-mediated immune response. To clarify this problem, we analyzed the expression levels of PD-1, PD-L1, and PD-L2 and immune function in antigen-specific T cell as derived from MTB patients or spleen lymphocytes derived from wild-type and PD-1 knockout mice with MTB antigen stimulation and Lewis lung cancer cells injection. Our data indicate that the expression levels of PD-1, PD-L1, and PD-L2 were elevated in active pulmonary TB patients, as well as in mice received MTB and lung cancer cells treatment. We also observed the T cell-mediated cellular immune response were inhibited by MTB while MTB significantly promote tumor metastasis in lung. In conclusion, the PD-1/PD-L pathway is required MTB repressed T-cell immune response and promotes tumor metastasis. This study provides evidence that blockade of PD-1/PD-L1 signaling pathway may benefit patients with MTB or other chronic infection and even prevent them from development of cancer.