Fig. 3

Lipid metabolism landscape in TME. Tumor cells have the ability to educate TME cells into a pro-tumor phenotype by secreting metabolites and signaling molecules, such as cytokines and bioactive lipids, to TME, which further facilitates cancer progression. For instance, CAFs activated by tumor cells lead to increased levels of lipid synthesis, which serve as an essential energy source for tumor cells and induce the formation of an immunosuppressive microenvironment through secreting EVs and signaling molecules. Besides, tumor-infiltrating CD8⁺ T cells and NK cells also exhibited increased lipid uptake and FAO. Similarly, lipid accumulation in TAMs also regulates their polarization and functional phenotypes. Increased lipid uptake and FAO in immunosuppressive cells, such as Tregs and MDSCs, further enhanced their pro-tumor effects. Taken together, lipid metabolic reprogramming facilitates crosstalk between tumor cells and TME cells, fueling tumor cells and changing functional phenotypes of TME cells