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靶向线粒体的策略在肿瘤免疫中的应用

英文原题:Mitochondria-targeted strategies in tumor immunity.

查看英文原题

Mitochondria-targeted strategies in tumor immunity.

PubMed 2025/10/30(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

线粒体作为细胞能量产生和代谢的调节因子,在肿瘤生长和存活中发挥着至关重要的作用。肿瘤通过Warburg效应被重编程以适应快速增殖。这种重编程导致乳酸和酮体等代谢产物的积累,从而降低肿瘤微环境的pH值,抑制效应T细胞和NK细胞的活性,同时促进调节性T细胞和MDSCs的浸润,形成免疫抑制微环境。线粒体产生的ROS可通过调节免疫细胞的信号通路影响其功能。线粒体还释放DAMPs,激活树突状细胞的抗原呈递能力并启动抗肿瘤免疫应答。目前,已采用多种方法,如DLCs修饰和线粒体靶向递送,使药物能够穿透脂质双层并进入线粒体,从而有助于减少肿瘤微环境中的免疫抑制。在本综述中,我们将讨论线粒体对肿瘤免疫的影响、靶向肿瘤细胞线粒体的策略,以及发现线粒体靶向药物以增强肿瘤免疫的进展,为开发新的癌症治疗策略提供潜在方向。

展开英文摘要原文

Mitochondria, as regulators of cellular energy production and metabolism, play a crucial role in tumor growth and survival. Tumors are reprogrammed to accommodate rapid proliferation through the Warburg effect. This reprogramming leads to the accumulation of metabolites such as lactate and ketone bodies, thereby lowering the pH of the tumor microenvironment, inhibiting the activity of effector T cells and NK cells, while promoting the infiltration of regulatory T cells and MDSCs, forming an immunosuppressive microenvironment. ROS produced by mitochondria can affect immune cell function by modulating their signaling pathways.

Mitochondria also release DAMPs, which activate the antigen-presenting capacity of dendritic cells and initiate anti-tumor immune responses. Currently, various methods have been employed, such as DLCs modifications and mitochondrial targeted delivery, which enable drugs to penetrate the lipid bilayer and enter the mitochondria, thereby helping to reduce immunosuppression in the tumor microenvironment.

In this review, we will discuss the impact of mitochondria on tumor immunity, strategies to target tumor cell mitochondria, and progress on the discovery of mitochondria-targeted drugs to enhance tumor immunity, providing potential directions for developing new cancer therapeutic strategies.

论文信息

作者
Cheng X、Wang Y、Johnson B、You M
第一作者单位
Department of Pharmacy, Suzhou Traditional Chinese Medicine (TCM) Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.China
通讯作者单位
Center for Cancer Prevention, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Weill Cornell Medicine, Houston, TX, United States.United States
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 41246345 · DOI 10.3389/fimmu.2025.1646138