Abstract
Simple SummaryThe 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.
Highlights
Cancer biology has been studied for many decades, and various factors that define the progression of cancer have been outlined as hallmarks of cancer [1]
A study by Su et al discusses the influence of CD36 mediated enhanced lipid uptake, accumulation, and metabolism in macrophages, which results in a differentiation into a tumor-associated macrophage (TAM)-phenotype
We reviewed the influence of Lipid droplets (LD) mediated storage and metabolism of fatty acids influencing the immune response mediated by myeloid cells [57], TAMs [55], and T cells [32]
Summary
A study by Su et al discusses the influence of CD36 mediated enhanced lipid uptake, accumulation, and metabolism in macrophages, which results in a differentiation into a tumor-associated macrophage (TAM)-phenotype They reported a direct relation between increased fatty acid oxidation and upregulation of Signal Transducer and Activator of Transcription (STAT6) phosphorylation, in turn promoting the immunosuppressive TAM phenotype [38]. All these reports show that LDs in mammalian immune cells, such as neutrophils and macrophages, play an important role in inflammatory or infectious processes, as increased LD accumulation appears to be linked directly to increased type I IFN response and LD surface is recognized as a site for Toll like receptor (TLR-7) and 9 signaling [70] These reports indicate the importance of dysregulated fatty acid metabolism in MDSCs, macrophages, and TAMs within TME with a prime focus on LD mediated fatty acid metabolism. We review and summarize the importance of understanding LD biology in order to find potential therapeutic targets for treating cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
