Fig. 3
The complex interaction of cells in the TME: CD8+ T cells kill cancer cells by promoting ferroptosis. Ferroptotic cancer cells release damage-associated molecular patterns (DAMPs), inducing the maturation of DCs and enhancing immune response. Activated APCs like DCs and macrophages reduce Cys2 into Cys to supply CD8+ T cells for GSH synthesis. MDSCs with a powerful intracellular storage capacity of Cys2 compete with APCs for Cys2, promoting T cell ferroptosis. CAFs are principal donor cells of GSH for cancer cells to help cancer cells fight ferroptosis and resist chemotherapy drugs like Pt. CAFs also secrete exosome-miR-522 to inhibit ALOX15 translation in cancer cells. CD8+ T cells promote GGT5 and interfere with system Xc− expression reducing GSH supplements for cancer cells