Fig. 4
From: Lipid metabolism in tumor-infiltrating regulatory T cells: perspective to precision immunotherapy
Lipid accumulation amplifies Treg suppression function. CD36 is up-regulated in both Teffs and Tregs, and the uptake of oxidized low-density lipoprotein (OxLDL) by CD36 leads to lipid peroxidation-mediated mitochondrial destruction, which interferes with metabolism and promotes cell senescence. Tregs effectively prevent lipid peroxidation by upregulating GPX4 and ensuring a high level of lipid metabolism. Apoptotic tumor cells promote mevalonate pathway-dependent cholesterol synthesis and CTLA-4 expression in Tregs by activating the PD1-PTEN signaling pathway. IDO receptor activation potentiates PD1-mediated PTEN activation. Lipids and SCFAs in TME promote the expression of Foxp3. Foxp3 promotes the expression of the PD1 gene by promoting the nuclear translocation of NFAT1. In addition, Foxp3 maintained the high level of cAMP and activated the mevalonate pathway through cAMP/PKA-SREBP1 to increase cholesterol level and CTLA-4 expression