SIRT1 Limits the Function and Fate of Myeloid-Derived Suppressor Cells in Tumors by Orchestrating HIF-1α-Dependent Glycolysis
SIRT1 Limits the Function and Fate of Myeloid-Derived Suppressor Cells in Tumors by Orchestrating HIF-1α-Dependent Glycolysis
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DOI：
10.1158/0008-5472.can-13-2584
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发表时间：
2014-02-01
期刊：
影响因子：
11.2
通讯作者：
Chu, Yiwei
中科院分区：
文献类型：
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作者：
Liu, Guangwei;Bi, Yujing;Chu, Yiwei
髓源性抑制细胞（MDSC）表现出不成熟的表型，可能在肿瘤中表现为经典活化（M1）或选择性活化表型（M2）。在这项研究中，我们研究了MDSCs分化为M1或M2骨髓谱系的代谢机制及其对癌症病理生理的影响。我们发现，当细胞从骨髓进入外周时，MDSCs中的SIRT1缺陷会导致M1谱系的特异性转换，从而降低抑制功能，有利于与肿瘤细胞攻击相关的促炎M1表型。通过mtor -缺氧诱导因子1a （HIF-1 α）途径激活糖酵解是M1表型分化所必需的，M1表型具有抗肿瘤的保护作用。我们的研究结果确定了SIRT1-mTOR/HIF-1 α糖酵解途径在决定MDSC分化中的本质，这对代谢重编程作为一种癌症治疗方法具有重要意义。(c) 2013年aacr。
Myeloid-derived suppressor cells (MDSC) display an immature phenotype that may assume a classically activated (M1) or alternatively activated phenotype (M2) in tumors. In this study, we investigated metabolic mechanisms underlying the differentiation of MDSCs into M1 or M2 myeloid lineage and their effect on cancer pathophysiology. We found that SIRT1 deficiency in MDSCs directs a specific switch to M1 lineage when cells enter the periphery from bone marrow, decreasing the suppressive function in favor of a proinflammatory M1 phenotype associated with tumor cell attack. Glycolytic activation through the mTOR-hypoxia-inducible factor1a (HIF-1 alpha) pathway was required for differentiation to the M1 phenotype, which conferred protection against tumors. Our results define the essential nature of a SIRT1-mTOR/HIF-1 alpha glycolytic pathway in determining MDSC differentiation, with implications for metabolic reprogramming as a cancer therapeutic approach. (C) 2013 AACR.