Fig. 3

The interaction between MΦs and tumor cells in the TME and details of the ferroptosis pathway in tumor cells (by Figdraw). A MΦs engulf red blood cells and digest them into hemoglobin, which is further degraded into heme. Heme is catabolized into Fe(III) and Fe(III), which are released from MΦs or promote ROS production, leading to ferroptosis. B Ferroptotic cell death is induced by the inhibition of system Xc⁻, resulting in the abrogation of GSH biosynthesis and inactivation of GPX4, which subsequently cause cell death through excess lipid ROS production. PUFAs-OOH and Fe(II) facilitate tumor cell ferroptosis mediated by the Fenton reaction. (ROS: reactive oxygen species; system Xc⁻: cystine–glutamate antiporter; GSH: glutathione; GPX4: glutathione peroxidase 4; and RBC: red blood cell.)