Fig. 3. The interaction of ferroptosis and lipid metabolism in modulating tumor immunity.

With the catalysis of ACSL4, LPCAT3, and 15-LOX, AA/AdA is oxidized to LPO that initiate ferroptosis. Some AA/AdA metabolites e.g., HETEs released from ferroptotic cancer cells activate antitumor immunity, while other lipids e.g., PGE₂ suppress immunity to promote tumor cell evasion. Immune cells also regulate the ferroptosis of cancer cells. Immunotherapy-activated CD8⁺ T cells induce the ferroptosis of cancer cells by releasing IFNγ to downregulate the system ${\mathrm{x}}_{\mathrm{c}}^{\text{-}}$. Thus, GSH level in tumor cells is not enough to eliminate LPO by GPX4, which leads to ferroptosis. Under certain conditions, immune cells including T cells, B cells, macrophages also undergo ferroptosis, which will modulate the tumor immunity