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CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer

2017; Landes Bioscience; Volume: 6; Issue: 6 Linguagem: Inglês

10.1080/2162402x.2017.1320011

2162-402X

Jieyao Li, Liping Wang, Xinfeng Chen, Lifeng Li, Yu Li, Ping Yü, Lan Huang, Dongli Yue, Zhen Zhang, Fei Wang, Feng Li, Yang Li, Jianmin Huang, Shuangning Yang, Hong Li, Xuan Zhao, Wenjie Dong, Yan Yan, Song Zhao, Bo Huang, Bin Zhang, Yi Zhang,

Immune Cell Function and Interaction

CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11b+CD33+ 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.