Fig. 4

Various metabolism process exists in TME, including lipid, amino acid, and glucose metabolism. Cholesterol in TME induces CD36 overexpression in T cells to promote the absorption of PUFAs, Ox-LDL, and Ox-PL in cells, fueling the ferroptosis of Tregs and CD8⁺ T cells. However, CD36 expression on Tregs maintains mitochondrial fitness to protect them from ferroptosis. Intensive glycolysis of cancer cells in TME leads to glucose starvation. It dictates ferroptosis resistance by activating the AMPK pathway to improve the MUFAs proportion of cell membrane and inducing over-expression of PDK4 to repress the TCA cycle and activity of ALOX. Lactic acid is taken in cancer cells and activates the AMPK pathway and ACSL4 to inhibit ferroptosis. Gln has recently been thought of as the leading energy metabolism resource participating in TCA and FA synthesis by glutaminolysis. Gln metabolism antagonizes with system Xc⁻ antioxidation function