细胞生物学
自噬
调解人
免疫系统
髓源性抑制细胞
调节器
生物
信号转导
髓样
癌症研究
化学
功能(生物学)
抑制器
免疫学
生物化学
基因
细胞凋亡
作者
Hemn Mohammadpour,Cameron R. MacDonald,Philip L. McCarthy,Scott I. Abrams,Elizabeth A. Repasky
出处
期刊:Cell Reports
[Elsevier]
日期:2021-10-01
卷期号:37 (4): 109883-109883
被引量:47
标识
DOI:10.1016/j.celrep.2021.109883
摘要
Myeloid-derived suppressor cells (MDSCs) impede antitumor immunity; however, the precise mechanisms that regulate their suppressive function remain unresolved. Identifying these mechanisms could lead to therapeutic interventions to boost cancer immunotherapy efficacy. Here, we reveal that β2 adrenergic receptor (β2-AR) expression on MDSCs increases with tumor growth and that the β2-AR stress pathway drives the immune suppressive activity of MDSCs by altering their metabolism. We show that β2-AR signaling decreases glycolysis and increases oxidative phosphorylation and fatty acid oxidation (FAO). It also increases expression of the fatty acid transporter CPT1A, which is necessary for the FAO-mediated immunosuppressive function of MDSCs. Moreover, we show that β2-AR signaling increases autophagy and activates the arachidonic acid cycle, both required for increasing the release of the immunosuppressive mediator, PGE2. Our data reveal that β2-AR signaling triggered by stress is an important physiological regulator of key metabolic pathways in MDSCs, driving their immunosuppressive function.
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