Emerging roles of ferroptosis in the tumor immune landscape: from danger signals to anti-tumor immunity.

Abstract

Regulated cell death (RCD) is a vital event in various physiological and pathological processes. Ferroptosis is a newly described RCD, which is driven by iron accumulation and unrestricted lipid peroxidation. The interaction between ferroptosis and immunity has been a topic of substantial interest since its discovery in 2012. It has become increasingly evident that ferroptosis is critically involved in the regulation of antitumor immunity and may provide potential strategies in immunotherapy. Ferroptosis could release various damage-associated molecular patterns (DAMPs) or lipid metabolites to regulate the cellular immune response, validating its role as a form of immunogenic cell death (ICD). Specifically, the oxygenated membrane lipids on ferroptotic cells could mediate the phagocytosis by macrophages to maintain the immune responses. Additionally, immune checkpoint inhibitor therapy may sensitize cancer cells to ferroptosis, while ferroptosis might contribute to tumor immune evasion by directly interfering with the function of various immune cells. Based on these insights, we provided a comprehensive review on the interaction patterns between ferroptosis and immunity, which may not only offer insight into the underlying regulatory mechanisms but also facilitating the development of ferroptosis-based antitumor therapeutics.