Fig. 5
From: Cold and hot tumors: from molecular mechanisms to targeted therapy
illustrates the dual role of ferroptosis in the tumor microenvironment. Concerning antitumor immunity, ferroptotic tumor cells release immunostimulatory signals that facilitate dendritic cell maturation, activate M1-polarized macrophages, and enhance T cell infiltration and activity within tumors. Both CD8+ T cells and neutrophils contribute to promoting ferroptosis in tumor cells. Ferroptosis in tumor cells alleviates the inhibition of cancer-associated fibroblasts (CAFs) by reducing TGF-b1 levels. Moreover, ferroptosis induction in various immunosuppressive cells, such as tumor-infiltrating neutrophils, myeloid-derived suppressor cells (MDSCs), regulatory T (Treg) cells, and M2-polarized tumor-associated macrophages (TAMs), boosts antitumor immunity. On the other hand, in terms of immunosuppression, ferroptotic tumor cells impede dendritic cell maturation through products of phospholipid peroxidation. Additionally, CXCL10 and HMGB1 released by ferroptotic cancer cells upregulate PD-L1 expression. The release of oxidized phospholipids and prostaglandin E2 (PGE2) by ferroptotic polymorphonuclear-MDSCs suppresses the function of CD8+ T cells. Furthermore, ferroptosis induction in various antitumor immune cells, including natural killer (NK) cells, B cells, and T follicular helper (TFH) cells, leads to inhibited antitumor immunity. In this context, black arrows represent promotion, while black bars symbolize inhibition. This figure was created using Figdraw
