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铁死亡与免疫治疗:突破肿瘤治疗耐药的屏障

英文原题:Ferroptosis and immunotherapy: Breaking barriers in cancer treatment resistance.

查看英文原题

Ferroptosis and immunotherapy: Breaking barriers in cancer treatment resistance.

PubMed 2025/08/19(内容时间) Crit Rev Oncol Hematol Q1 · IF 6.2(JCR 2025)

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中文摘要

免疫治疗革新了癌症治疗,但其疗效常受肿瘤微环境中的内在或获得性耐药机制限制。铁死亡是一种由铁依赖性脂质过氧化驱动的调控性细胞死亡,近期成为克服这些治疗障碍的有力策略。本综述探讨铁死亡与免疫应答之间的动态相互作用,重点介绍铁死亡如何调节巨噬细胞极化、T 细胞活性和细胞因子信号,从而重塑免疫抑制性肿瘤环境。诱导铁死亡可增强肿瘤免疫原性、促进 T 细胞浸润,并使耐药癌细胞对免疫检查点抑制剂、CAR-T 和单克隆抗体更敏感。此外,靶向铁死亡通路可破坏由调节性 T 细胞和髓源性抑制细胞介导的免疫逃逸机制,进一步增强免疫治疗结局。本文解析铁死亡的分子和代谢基础及其与免疫策略的整合,强调其克服癌症免疫治疗耐药、推动创新联合治疗的潜力。

展开英文摘要原文

Cancer treatment has been revolutionized by immunotherapy; however, its efficacy is often hindered by intrinsic or acquired resistance mechanisms within the tumor microenvironment. Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has recently emerged as a potent strategy to overcome these therapeutic barriers.

This review explores the dynamic interplay between ferroptosis and immune responses, highlighting how ferroptosis modulates macrophage polarization, T cell activity, and cytokine signaling to reshape the immunosuppressive tumor milieu. The induction of ferroptosis enhances tumor immunogenicity, facilitates T cell infiltration, and sensitizes resistant cancer cells to immune checkpoint inhibitors, CAR T-cell therapy, and monoclonal antibodies.

Additionally, targeting ferroptosis pathways disrupts immune escape mechanisms mediated by regulatory T cells and myeloid-derived suppressor cells, further augmenting immunotherapeutic outcomes. By dissecting the molecular and metabolic underpinnings of ferroptosis and its integration with immune strategies, this article underscores its potential to overcome cancer immunotherapy resistance and pave the way for innovative combinatorial treatments.

论文信息

作者
Ebrahimnezhad M、Valizadeh A、Yousefi B
第一作者单位
Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: mohamad.ibrahimnezhad@gmail.com.Iran
通讯作者单位
Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: bahmanusefi@gmail.com.Iran
文献类型
综述
期刊
Critical reviews in oncology/hematology2025 Oct
原文标识
PubMed 40840639 · DOI 10.1016/j.critrevonc.2025.104907