Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China.
Cell Death Dis. 2019 Jan 18;10(2):44. doi: 10.1038/s41419-018-1237-y.
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.
鉴于世界上有三分之一的人口感染了结核分枝杆菌（MTB），因此了解 MTB 感染与肺癌之间的潜在分子机制非常重要。本研究通过 T 细胞介导的免疫反应，研究了 MTB 感染对肺癌细胞肺转移的免疫反应。为了阐明这一问题，我们分析了源自 MTB 患者或源自野生型和 PD-1 敲除小鼠的脾淋巴细胞的抗原特异性 T 细胞中的 PD-1、PD-L1 和 PD-L2 的表达水平及其免疫功能，这些细胞经 MTB 抗原刺激和 Lewis 肺癌细胞注射。我们的数据表明，在活动性肺结核患者以及接受 MTB 和肺癌细胞治疗的小鼠中，PD-1、PD-L1 和 PD-L2 的表达水平升高。我们还观察到 MTB 抑制了 T 细胞介导的细胞免疫反应，同时 MTB 显著促进了肺转移。总之，PD-1/PD-L 通路是 MTB 抑制 T 细胞免疫反应和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 信号通路可能使 MTB 或其他慢性感染患者受益，甚至可以预防他们发生癌症。
