Ferroptosis and Cancer Immunotherapy

Abstract: Traditional treatment strategies for cancer are unsatisfactory. As a nonapoptotic cell death process and owning to the characteristics of iron-dependent lipid peroxide accumulation, ferroptosis has become a new target of tumor treatment. Numerous studies have proved that ferroptosis could enhance the immunogenicity of cancer and interact with immune cells. Cancer antigens, exposed to cancer cells that underwent ferroptosis, effectively improve the immunogenicity of the tumor microenvironment and promote the activation and maturation of immune cells. Meantime, immune cells release immunostimulatory cytokines including TNF-α and IFN-γ to downregulate the expression of SLC7A11 and SLC3A2, and reduce the absorption of cysteine, leading to lipid peroxidation and iron deposition in cancer cells. Consequently, induction of ferroptosis via iron deposition-based combination strategies could stimulate and activate natural and adaptive immune responses which release immune-stimulating factors to induce iron deposition in cancer cells. In this review, we provided a critical analysis of the correlation between ferroptosis and the immune responses, providing a novel way to effectively induce ferroptosis in cancer, which may be one of the focuses in future to improve the development of new therapeutic strategies of cancer.