Fig. 4

Mechanism of lipid metabolic reprogramming in immune cells. A hypoxic, glucose-deficient, lipid-rich TME often educates immune cells into an immunosuppressive and pro-tumor phenotype by reprogramming their lipid metabolism. Immune cells in the TME undergo lipid metabolism reprogramming by directly absorbing excess lipids in the TME or enhancing their own lipid uptake, synthesis, and oxidation. Overexpression of PD-1 and CD36 on CD8⁺ TILs promotes metabolic transition by activating STAT3 or PPARs, which results in enhanced FAO (a). In Tregs cells, lipid metabolism is enhanced by CD36-PPARβ signaling, AKT-mTORC1 signaling, and SREBPs-mediated overexpression of FASN (b). TAMs can use lipids directly in TME or uptake exosomes containing LCFAs. FAO in TAMs is also enhanced by CD36-PPARs signaling (c). In DCs, NK cells, and MDSCs, CD36-PPARs signaling also plays a critical role in modulating their lipid metabolism (d–f)