Lipid Metabolic Pathways Confer the Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor.

Dehong Yan,Adeleye O Adeshakin,Guizhong Zhang,Meichen Xu,Xiaochun Wan,Youhai H Chen,Lukman O Afolabi

doi:10.3389/fimmu.2019.01399

Abstract

Myeloid-derived suppressor cells (MDSCs) play crucial roles in tumorigenesis and their inhibition is critical for successful cancer immunotherapy. MDSCs undergo metabolic reprogramming from glycolysis to fatty acid oxidation (FAO) and oxidative phosphorylation led by lipid accumulation in tumor. Increased exogenous fatty acid uptake by tumor MDSCs enhance their immunosuppressive activity on T-cells thus promoting tumor progression. Tumor-infiltrating MDSCs in mice may prefer FAO over glycolysis as a primary source of energy while treatment with FAO inhibitors improved anti-tumor immunity. This review highlights the immunosuppressive functions of lipid metabolism and its signaling pathways on MDSCs in the tumor microenvironment. The manipulation of these pathways in MDSCs is relevant to understand the tumor microenvironment therefore, could provide novel therapeutic approaches to enhance cancer immunotherapy.

Highlights

Myeloid-derived suppressor cells (MDSCs) are pathologically activated cells displaying an exceptional immunosuppressive ability [1, 2]
Since apolipoprotein E (ApoE) plays a crucial role in lipoprotein metabolism [69], its deletion could enhance MDSCs immunosuppressive activity on T-cells via lipid accumulation
Since mTORC2 can regulate lipid metabolism by limiting the activity of ATP citrate lyase (ACLY) to generate the building blocks of lipids, targeting this signaling pathway could attenuate the immunosuppressive activities of MDSCs

Summary

Introduction

Myeloid-derived suppressor cells (MDSCs) are pathologically activated cells displaying an exceptional immunosuppressive ability [1, 2]. They showed that targeting ACC1 with 5- (tetradecycloxy)-2-furoic acid (TOFA), reverses the effects immunosuppressive activity of PMN-MDSCs. Collectively, these studies suggest the critical role of oxidized lipids in regulating myeloid cells function and in MDSC as a potential therapeutic target in cancer.

Results

Conclusion