Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province 210093, PR China.
Biomed Pharmacother. 2023 Sep;165:115251. doi: 10.1016/j.biopha.2023.115251. Epub 2023 Jul 31.
Ferroptosis, an established form of programmed cell death discovered in 2012, is characterized by an imbalance in iron metabolism, lipid metabolism, and antioxidant metabolism. Activated CD8 + T cells can trigger ferroptosis in tumor cells by releasing interferon-γ, which initiates the ferroptosis program. Despite the remarkable progress made in treating various tumors with immunotherapy, such as anti-PD1/PDL1, there are still significant challenges to overcome, including limited treatment options and drug resistance. In this review, we exam the potential biological significance of the ferroptosis phenotype using bioinformatics and review the latest advancements in understanding the mechanism of ferroptosis-mediated anti-tumor immunotherapy. Furthermore, we revisit the host immune system, immune microenvironment, ferroptotic defense system, metabolic reprogramming, and key genes that regulate the occurrence and resistance of ferroptosis of tumor cell. Additionally, several immune-combined ferroptosis treatment strategies were put forward to improve immunotherapy efficacy and to provide new insights into reversing anti-tumor immune drug resistance.
铁死亡是 2012 年发现的一种程序性细胞死亡方式，其特征是铁代谢、脂质代谢和抗氧化代谢失衡。激活的 CD8+T 细胞可以通过释放干扰素-γ触发肿瘤细胞中的铁死亡，从而启动铁死亡程序。尽管免疫疗法在治疗各种肿瘤方面取得了显著进展，如抗 PD1/PDL1，但仍面临着重大挑战，包括治疗选择有限和耐药性。在这篇综述中，我们使用生物信息学方法研究了铁死亡表型的潜在生物学意义，并综述了理解铁死亡介导的抗肿瘤免疫治疗机制的最新进展。此外，我们重新审视了宿主免疫系统、免疫微环境、铁死亡防御系统、代谢重编程以及调控肿瘤细胞铁死亡发生和耐药性的关键基因。此外，还提出了几种免疫联合铁死亡治疗策略，以提高免疫治疗的疗效，并为逆转抗肿瘤免疫药物耐药性提供新的思路。
