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CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-?-mTOR-HIF-1 signaling in patients with non-small cell lung cancer #MMPMID28680754
Li J; Wang L; Chen X; Li L; Li Y; Ping Y; Huang L; Yue D; Zhang Z; Wang F; Li F; Yang L; Huang J; Yang S; Li H; Zhao X; Dong W; Yan Y; Zhao S; Huang B; Zhang B; Zhang Y
Oncoimmunology 2017[]; 6 (6): ä PMID28680754show ga
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-? 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-? triggered phosphorylation of mammalian target of rapamycin, and subsequently activated hypoxia-inducible factor-1? (HIF-1?) 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.