Fig. 3

Macrophage metabolic targets and associated Agents. Targeting the metabolic reprogramming of TAMs has the potential to reshape their phenotype and function, thereby offering a promising therapeutic strategy for macrophage repolarization in cancer. The fundamental approach in treating tumors via TAM metabolic reprogramming involves stimulating TAMs towards an M1-like pro-inflammatory phenotype. This strategy includes regulating intracellular ATP levels and redox state, which in turn impacts their phagocytic and digestive abilities and the generation of various signaling molecules, while simultaneously inhibiting M2-like anti-inflammatory polarization. Despite the growing interest in targeting TAM metabolism, our current understanding of TAM metabolic reprogramming is still incomplete, and there remains a dearth of specific targeted therapeutics. Future investigations should focus on exploring the metabolic mechanisms of reprogramming within specific subgroups, in the context of single-cell multi-omics studies, to identify unique therapeutic targets. ETC Electron Transport Chain, IDO Indoleamine 2,3-dioxygenase, GS Glutamine Synthetase, LXR Liver X receptor, ABCA1 ATP-binding cassette transporter A1, IRG1 Immune Responsive Gene 1, ACOD1 Aconitate Decarboxylase 1, TLR9 Toll-Like Receptor 9, Arg1 Arginase 1, HADCs Histone Deacetylases