靶向癌症中的线粒体转移轴：从机制的见解到治疗的重新布线

摘要(中文译文)

细胞间线粒体转移正逐渐成为癌症治疗的一个靶点。它驱动着一个双向的代谢-免疫轴，促进肿瘤进展和免疫逃逸。本综述将癌症视为一个被重编程的线粒体生态系统。在该生态系统中，正向转移（基质→癌细胞）促进增殖和治疗耐药，而反向转移（癌细胞→免疫细胞）则诱导T细胞耗竭。我们强调宿主代谢（如肥胖）是关键调节因素。在治疗方面，我们描绘了从抑制有害转移（如靶向Miro1/USP30）向主动向免疫细胞递送功能性线粒体的转变。整合空间多组学、人工智能和先进成像技术将实现以线粒体为核心的精准肿瘤学。该方法超越了单纯的抑制，转向对肿瘤微环境的主动重塑。本综述为靶向线粒体转移以破坏肿瘤-基质-免疫串扰并增强治疗效果提供了药理学路线图。

Abstract

Intercellular mitochondrial transfer is emerging as a therapeutic target in cancer. It drives a bidirectional metabolic-immune axis that fuels tumor progression and immune evasion. This review frames cancer as a rewired mitochondrial ecosystem. In this ecosystem, forward transfer (stroma→cancer) fuels proliferation and therapy resistance, while reverse transfer (cancer→immune) induces T-cell exhaustion. We highlight host metabolism (e.g., obesity) as a key modulator. Therapeutically, we chart a shift from inhibiting detrimental transfer (e.g., targeting Miro1/USP30) toward actively delivering functional mitochondria to immune cells. Integrating spatial multi-omics, AI, and advanced imaging will enable mitochondria-centric precision oncology. This approach moves beyond inhibition to active remodeling of the tumor microenvironment. This synthesis provides a pharmacological roadmap for targeting mitochondrial transfer to disrupt tumor-stroma-immune crosstalk and enhance therapeutic efficacy.

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