ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells.
10.1016/j.apsb.2023.09.005
- Author:
Mingjin WANG
1
;
Weida WANG
1
;
Shen YOU
1
;
Zhenyan HOU
1
;
Ming JI
1
;
Nina XUE
1
;
Tingting DU
1
;
Xiaoguang CHEN
1
;
Jing JIN
1
Author Information
1. Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
Acetyl-CoA acetyltransferase 1;
CXCL1;
Glioblastoma;
Lipid metabolism;
Macrophages;
Myeloid cells;
Myeloid-derived suppressor cells;
Tumor microenvironment
- From:
Acta Pharmaceutica Sinica B
2023;13(12):4733-4747
- CountryChina
- Language:English
-
Abstract:
Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C-X-C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.
