Fig. 2: Metabolic interplay between tumor cells and TAMs within TME.
From: Metabolic guidance and stress in tumors modulate antigen-presenting cells
Lactate transported by MCT1 and GPCRs (e.g., OLFR78 and GPR132) shapes pro-tumoral properties of TAMs by upregulating M2-associated genes. Enrichment of TCA cycle metabolites affects the metabolic properties of TAMs. SUCNR1-mediated succinate uptake activates PI3K-HIF1α signaling to induce polarization of TAMs. Furthermore, accumulation of kynurenine within TAMs generated from tryptophan and 2-HG (generated by mutant IDH on tumor cells) by sequential activities of IDO and TDO, binds to aryl hydrocarbon receptor (AhR), and suppresses NF-κB signaling. Glutaminolysis produce α-ketoglutarate (αKG), supplying intermediate for the TCA cycle, and further alters the epigenome of macrophages. Increased dependency on fatty acid oxidation (FAO) or ER stress induced by lipids enriched in TME leads macrophages to adopt pro-tumoral characteristics.
