Data from SIRT1 Limits the Function and Fate of Myeloid-Derived Suppressor Cells in Tumors by Orchestrating HIF-1α–Dependent Glycolysis
Year: 2023
Type: other
Abstract: 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 factor-1α (HIF-1α) 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-1α glycolytic pathway in determining MDSC differentiation, with implications for metabolic reprogramming as a cancer therapeutic approach. Cancer Res; 74(3); 727–37. ©2013 AACR.
Authors: Guangwei Liu, Yujing Bi, Bo Shen, Hui Yang, Yan Zhang, Xiao Wang, Huanrong Liu, Yun Lu, Jiongbo Liao, Xi Chen, Yiwei Chu
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4392687770