Fig. 1

Metabolic reprogramming in the tumor microenvironment. In the tumor microenvironment, most of the glucose and oxygen transported by disorganized blood vessels are taken up by tumor cells, leading to hypoxia and a glucose-deprived microenvironment. Activated glycolysis in tumor cells generates increased lactic acid but still does not satisfy energy needs. As a result, LPL from tumor cells and other stromal cells activates adipocytes and induces lipolysis of stored triglycerides and secretion of FAs, which are transported into cells through CD36 or FATPs. In addition, tumor cells can generate FAs via de novo synthesis pathway using acetyl-CoA from the catabolism of glucose. ACC and FASN participate in this process. These FAs then participate in FAO or other signaling pathways to produce many immunosuppressive factors or generate LDs. In addition, lipoproteins in the TME are transported via lipoprotein receptors (LRs) and catabolize to cholesterol in cells. Tumor cells can also generate cholesterol via the mevalonate pathway. Dysregulated lipid metabolism in tumor cells promotes the formation of acidic, hypoxic, glucose-deprived, and lipid-rich immunosuppressive microenvironments