Metabolic reprogramming in macrophage responses

Macrophages are critical mediators of tissue homeostasis, with the function of tissue development and repair, but also in defense against pathogens. Tumor-associated macrophages (TAMs) are considered as the main component in the tumor microenvironment and play an important role in tumor initiation, growth, invasion, and metastasis. Recently, metabolic studies have revealeded specific metabolic pathways in macrophages are tightly associated with their phenotype and function. Generally, pro-inflammatory macrophages (M1) rely mainly on glycolysis and exhibit impairment of the tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation (OXPHOS), whereas anti-inflammatory macrophages (M2) are more dependent on mitochondrial OXPHOS. However, accumulating evidence suggests that macrophage metabolism is not as simple as previously thought. This review discusses recent advances in immunometabolism and describes how metabolism determines macrophage phenotype and function. In addition, we describe the metabolic characteristics of TAMs as well as their therapeutic implications. Finally, we discuss recent obstacles facing this area as well as promising directions for future study.

Automated summary

Macrophages are key regulators of tissue homeostasis, involved in tissue development, repair, and defense against pathogens. TAMs play a crucial role in the tumor microenvironment, impacting tumor initiation, growth, invasion, and metastasis. The metabolic characteristics of macrophages influence their phenotype and function, with pro-inflammatory M1 macrophages relying on glycolysis and anti-inflammatory M2 macrophages more dependent on mitochondrial OXPHOS.