Fatty Acid Metabolism in Myeloid-Derived Suppressor Cells and Tumor-Associated Macrophages: Key Factor in Cancer Immune Evasion

Simple Summary The review article discusses metabolic changes in the tumor microenvironment (TME), which in turn influences the immune cell compartment modulating the phenotype and functionality of immune cells. The main focus is to discuss the influence of increased fatty acid content in the TME, storage of fatty acids in lipid droplet (LDs) organelles in myeloid-derived suppressor cells (MDSCs), macrophages, especially tumor-associated macrophages (TAMs) and resulting functional changes towards an immunosuppressive phenotype. Thus, defining the importance of understanding the role of LD organelles in identifying new therapeutic targets for targeting immunosuppression in cancer. The tumor microenvironment (TME) comprises various cell types, soluble factors, viz, metabolites or cytokines, which together play in promoting tumor metastasis. Tumor infiltrating immune cells play an important role against cancer, and metabolic switching in immune cells has been shown to affect activation, differentiation, and polarization from tumor suppressive into immune suppressive phenotypes. Macrophages represent one of the major immune infiltrates into TME. Blood monocyte-derived macrophages and myeloid derived suppressor cells (MDSCs) infiltrating into the TME potentiate hostile tumor progression by polarizing into immunosuppressive tumor-associated macrophages (TAMs). Recent studies in the field of immunometabolism focus on metabolic reprogramming at the TME in polarizing tumor-associated macrophages (TAMs). Lipid droplets (LD), detected in almost every eukaryotic cell type, represent the major source for intra-cellular fatty acids. Previously, LDs were mainly described as storage sites for fatty acids. However, LDs are now recognized to play an integral role in cellular signaling and consequently in inflammation and metabolism-mediated phenotypical changes in immune cells. In recent years, the role of LD dependent metabolism in macrophage functionality and phenotype has been being investigated. In this review article, we discuss fatty acids stored in LDs, their role in modulating metabolism of tumor-infiltrating immune cells and, therefore, in shaping the cancer progression.

Automated summary

This review article discusses the influence of metabolic changes in the tumor microenvironment on immune cells, with a focus on the role of fatty acids stored in lipid droplets. Understanding the importance of lipid droplets in modulating immune cell function and phenotype is crucial for identifying new therapeutic targets and addressing immunosuppression in cancer.