Models of ferroptosis in innate immune cells. (a) Ferroptosis in macrophages. The activation of the SLC7A110-GSH-GPX4 axis or an increase in iron storage protein ferritin by nuclear receptor coactivator 4–mediated ferritinophagy prevents lipid peroxidation in macrophages. In contrast, erythrophagocytosis or exogenous ferric ions can trigger iron-dependent ferroptosis in macrophages. Compared with M2 microglia/macrophages, M1 cells are resistant to ferroptosis due to the loss of ALOX15 activity by NOS2-mediated NO production. The released DAMPs (e.g., HMGB1, KRASG12D, and 8-OHG) by ferroptotic cancer cells cause inflammation-related immunosuppression through AGER- or STING1-mediated macrophage polarization. (b) Ferroptosis in neutrophils. The activation of NOX and PADI4 is essential for NET formation in neutrophils. The release of myeloperoxidase (MPO) by neutrophils through NET induces lipid peroxidation and subsequent ferroptosis in glioblastoma cells.