School of Life Science, Chongqing University, China.
FEBS J. 2022 Jul;289(13):3655-3665. doi: 10.1111/febs.16034. Epub 2021 Jun 11.
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.
细胞程序性死亡(RCD)是各种生理和病理过程中的一个重要事件。铁死亡是一种新描述的 RCD,其由铁积累和不受限制的脂质过氧化驱动。自 2012 年发现以来,铁死亡与免疫之间的相互作用一直是一个重要的研究课题。越来越明显的是,铁死亡在调节抗肿瘤免疫中起着关键作用,并可能为免疫治疗提供潜在的策略。铁死亡可以释放各种损伤相关分子模式(DAMPs)或脂质代谢物来调节细胞免疫反应,证实了它作为一种免疫原性细胞死亡(ICD)的形式。具体来说,铁死亡细胞上的含氧膜脂质可以介导巨噬细胞的吞噬作用,以维持免疫反应。此外,免疫检查点抑制剂治疗可能使癌细胞对铁死亡敏感,而铁死亡可能通过直接干扰各种免疫细胞的功能来促进肿瘤免疫逃逸。基于这些见解,我们对铁死亡与免疫之间的相互作用模式进行了全面综述,这不仅可以深入了解潜在的调节机制,还可以促进基于铁死亡的抗肿瘤治疗的发展。
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