非小细胞肺癌患者中通过转化生长因子-β-雷帕霉素靶蛋白-低氧诱导因子-1信号通路使髓源性抑制细胞上的CD39/CD73上调
CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer.
作者信息
Li Jieyao, Wang Liping, Chen Xinfeng, Li Lifeng, Li Yu, Ping Yu, Huang Lan, Yue Dongli, Zhang Zhen, Wang Fei, Li Feng, Yang Li, Huang Jianmin, Yang Shuangning, Li Hong, Zhao Xuan, Dong Wenjie, Yan Yan, Zhao Song, Huang Bo, Zhang Bin, Zhang Yi
机构信息
Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
出版信息
Oncoimmunology. 2017 Apr 21;6(6):e1320011. doi: 10.1080/2162402X.2017.1320011. eCollection 2017.
CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11bCD33 myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues from non-small cell lung cancer (NSCLC) patients expressed surface ectonucleotidases CD39 and CD73. Tumor TGF-β stimulated CD39 and CD73 expression, thereby inhibited T cell and NK cell activity, and protected tumor cells from the cytotoxic effect of chemotherapy through ectonucleotidase activity. Mechanistically, TGF-β triggered phosphorylation of mammalian target of rapamycin, and subsequently activated hypoxia-inducible factor-1α (HIF-1α) that induced CD39/CD73 expression on MDSCs. CD39 and CD73 on MDSCs, therefore, link their immunosuppressive and chemo-protective effects to NSCLC progression, providing novel targets for chemo-immunotherapeutic intervention.
CD39/CD73-腺苷途径最近被定义为一种重要的肿瘤诱导的免疫抑制机制。我们在此记录到，非小细胞肺癌（NSCLC）患者外周血和肿瘤组织中一部分CD11bCD33髓源性抑制细胞（MDSCs）表达表面外切核苷酸酶CD39和CD73。肿瘤转化生长因子-β（TGF-β）刺激CD39和CD73表达，从而抑制T细胞和自然杀伤（NK）细胞活性，并通过外切核苷酸酶活性保护肿瘤细胞免受化疗的细胞毒性作用。机制上，TGF-β触发雷帕霉素靶蛋白的磷酸化，随后激活缺氧诱导因子-1α（HIF-1α），后者诱导MDSCs上CD39/CD73的表达。因此，MDSCs上的CD39和CD73将它们的免疫抑制和化学保护作用与NSCLC进展联系起来，为化学免疫治疗干预提供了新的靶点。
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