Metabolic Reprogramming in Tumor-Associated Macrophages in the Ovarian Tumor Microenvironment

SIMPLE SUMMARY: The highly metastatic and immunosuppressive microenvironment of ovarian cancers is a major determinant of the aggressive nature and therapeutic resistance of ovarian cancer. Therefore, we believe that a thorough understanding of the mechanisms that regulate the composition and function of the tumor microenvironment is critical for the development of a more effective course of treatment for this devastating malignancy. This review summarizes the recent literature on the major metabolic pathways affecting macrophage immune metabolism and its impact on phenotypic and functional changes in macrophages in the ovarian tumor microenvironment. ABSTRACT: The interaction between tumor cells and macrophages in the tumor microenvironment plays an essential role in metabolic changes in macrophages and reprograms them towards a pro-tumorigenic phenotype. Increasing evidence indicates that macrophage metabolism is a highly complex process and may not be as simple as previously thought. Pro-inflammatory stimuli switch macrophages towards an M1-like phenotype and rely mainly on aerobic glycolysis and fatty acid synthesis, whereas anti-inflammatory stimuli switch macrophages towards an M2-like phenotype. M2-like macrophages depend more on oxidative phosphorylation (OXPHOS) and fatty acid oxidation. However, this metabolically reprogrammed phenotypic switch in macrophages remained a mystery for a while. Therefore, through this review, we tend to describe how macrophage immunometabolism determines macrophage phenotypes and functions in tumor microenvironments (TMEs). Furthermore, we have discussed how metabolic reprogramming in TAM can be used for therapeutic intervention and drug resistance in ovarian cancer.