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线粒体DNA介导的细胞间通信通过细胞外囊泡在低氧压力下驱动HCC进展

Jiaying Fu¹, Qingqing Liu¹, Yuan Yuan¹

¹Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, China.

|August 14, 2025

概括

肝细胞癌 (HCC) 中的缺氧通过细胞外囊泡 (EV) 释放线粒体DNA (mtDNA),促进免疫抑制瘤微环境. 这项研究揭示了EVs-mtDNA作为提高HCC免疫疗法的有效性的目标.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
细胞生物学细胞生物学

背景情况:

免疫疗法对肝细胞癌 (HCC) 是有前途的,但由于瘤的免疫抑制微环境,它面临着挑战.
瘤细胞中的异常线粒体DNA (mtDNA) 压力与细胞间通信有关,影响瘤及其微环境,尽管确切的机制尚不清楚.

研究的目的:

调查线粒体DNA (mtDNA) 在缺氧衍生的细胞外囊泡 (EV) 中的作用,这些囊泡调解巨细胞M2极化,并促进肝细胞癌 (HCC) 的进展.
阐明 mtDNA 通过哪些途径为 HCC 中的免疫抑制微环境作出贡献.
为潜在的治疗干预开发一个有针对性的纳米输送系统.

主要方法:

在体外和体内实验中进行了实验,以分析在低氧条件下的mtDNA释放.
研究了通过EVs进行线粒体质量控制 (MQC) 信号和外细胞形成.
研究了携带mtDNA的EVs对巨细胞中cGAS/STING/NF-κB通路的激活.
开发了一种纳米输送系统,用于有针对性的药物输送.

主要成果:

发现缺氧可以增强线粒体质量控制 (MQC) 信号,通过EVs促进mtDNA释放和exocytosis.
携带mtDNA的细胞外囊泡 (EVs) 已被证明可以激活巨细胞中的cGAS/STING/NF-κB通路.
这种激活导致巨细胞的M2表型极化,从而促进HCC的进展.
开发的纳米输送系统展示了瘤向能力,并在体内抑制了瘤生长.

结论:

细胞外囊泡介导的线粒体DNA (EVs-mtDNA) 在低氧条件下在肝细胞癌 (HCC) 中建立免疫抑制微环境中起着至关重要的作用.
这些发现揭示了一种涉及EVs-mtDNA在HCC进展和免疫抑制中的新途径.
这项研究提供了新的见解和潜在的治疗策略,包括有针对性的纳米输送系统,以改善HCC的免疫治疗敏感性.

关键词:

细胞外囊泡中的细胞外囊泡.缺氧缺氧是指缺氧的情况.巨细胞是一个巨细胞.这是线粒体DNA的DNA.瘤免疫微环境是一个微环境.

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