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靶向铁死亡用于癌症治疗:铁代谢与抗癌免疫

Targeting ferroptosis for cancer therapy: iron metabolism and anticancer immunity.

作者信息

Luo Lianxiang, Wang Han, Tian Wen, Zeng Jiayan, Huang Yuru, Luo Hui

机构信息

Southern Marine Science and Engineering Guangdong Laboratory Zhanjiang 524023, Guangdong, China.

The Marine Biomedical Research Institute, Guangdong Medical University Zhanjiang 524023, Guangdong, China.

出版信息

Am J Cancer Res. 2021 Nov 15;11(11):5508-5525. eCollection 2021.

Abstract

Ferroptosis is a new form of programmed cell death characterized by iron-dependent accumulation of lipid peroxidation, which plays an important role in cancer biology. Ferroptosis is involved in many biological processes, such as amino acid metabolism, glutathione metabolism, iron metabolism, and lipid metabolism. Iron is an essential trace element in a variety of normal cell processes, such as DNA synthesis and repair, cell respiration, metabolism and signal transduction, etc., and iron metabolism disorder has been considered as one of the metabolic markers of malignant cancer cells. In addition, iron is involved in the regulation of innate and adaptive immune responses, suggesting that targeted regulation of iron metabolism may contribute to anti-tumor immunity and cancer therapy. In this review, the regulatory mechanism of ferroptosis, the interaction between ferroptosis on tumor cell metabolism, and anti-tumor immunity were systematically reviewed. Immunotherapy combined with targeted regulation of iron and iron-dependent regulation of ferroptosis should be the focus of future ferroptosis research.

摘要

铁死亡是一种新的程序性细胞死亡形式,其特征是脂质过氧化的铁依赖性积累,在癌症生物学中发挥重要作用。铁死亡参与许多生物学过程,如氨基酸代谢、谷胱甘肽代谢、铁代谢和脂质代谢。铁是多种正常细胞过程中的必需微量元素,如DNA合成与修复、细胞呼吸、代谢和信号转导等,铁代谢紊乱被认为是恶性癌细胞的代谢标志物之一。此外,铁参与先天和适应性免疫反应的调节,这表明靶向调节铁代谢可能有助于抗肿瘤免疫和癌症治疗。在本综述中,系统综述了铁死亡的调控机制、铁死亡与肿瘤细胞代谢的相互作用以及抗肿瘤免疫。免疫疗法联合铁的靶向调节和铁依赖性铁死亡调节应是未来铁死亡研究的重点。

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