Fig. 2

Immune-related intracellular energy metabolism and substance synthesis. The diagram shows the metabolic activities and synthetic reactions that occur in the cell under enzymatic reactions and correlate with or might cause immune changes (enzymes are labeled in purple, nutrients or metabolites are labeled in green, molecules or targets are labeled in yellow, and inhibitors are labeled in grey). For example, lipid uptake from the TME leads to elevated intracellular cholesterol concentrations, which in turn triggers ER stress (inducing CD8⁺ T cell dysfunction). The PI3K/AKT pathway, which is activated by growth factor signals, stimulates the mTOR family molecules, which in turn elicits vital activities such as protein synthesis, cell proliferation, and autophagy, and so on. The mTOR family molecules are also regulated by amino acids. FA synthesis is coordinated sequentially by several enzymes involving ACC1 (inhibition of ACC1 reduces TH17 cell differentiation but enhances the formation of memory CD4+ T cells). And C75 inhibits FASN which in turn diminishes FA synthesis. In addition, the induction of FA oxidation was associated with an increase in AMPK activity (AMPK also promotes the generation of memory CD8⁺ T cells). JHU083 inhibited glutaminase-mediated glutaminolysis. TME, tumor microenvironment; SREBP, sterol regulatory element binding protein; ER, endoplasmic reticulum; PI3K, phosphatidylinositol 3-kinase; FA, Fatty acid; ACC1, acetyl-CoA carboxylase 1; PDH, pyruvate dehydrogenase; αKG, α-ketoglutarate; FASN, fatty acid synthase; AMPK, AMP-activated protein kinase