Figure 4.

Role of FABP5 in regulating lipid metabolism in different subsets of T cells. As the main lipid chaperone in T cells, FABP5 facilitates the uptake of exogenous fatty acids and de novo lipid synthesis, thus promoting mitochondrial FAO and membrane lipid synthesis, respectively. In general, FABP5 deficiency is associated with enhanced immune suppressive activity of Tregs and reduced survival of Trm and exhausted T cells in the TME, which contribute to elevated tumor growth in FABP5^-/- mice on the LFD. Notably, naïve T cells mainly rely on glucose for their survival, while uptake of exogenous fatty acids, especially LA, by FABP5 promotes mitochondrial ROS and lipid peroxidation, inducing naïve T cell death; thus, mice on HFD rich in LA exhibit reduced CD8⁺ T cells in the TME, leading to excecated tumor growth. The role of FABP5 in mediating lipid metabolism and function in other T cell subsets (e.g., Th17 or γδ T cells) in the TME needs further investigation.