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巨噬细胞脂质代谢:肿瘤微环境代谢枢纽与靶向干预策略,从机制探索到临床转化

Macrophage Lipid Metabolism: A Metabolic Hub in the Tumor Microenvironment and Novel Therapeutic Target, from Mechanistic Insights to Clinical Translation

  • 摘要: 肿瘤微环境中脂质代谢重编程是癌症进展的核心驱动力,而肿瘤相关巨噬细胞(TAM)作为关键枢纽,通过调控脂质摄取、存储与信号传递,塑造免疫抑制生态位并促进转移。本文系统综述:TAM脂质代谢机制包括,脂质吸收、胞内处理及代谢信号驱动TAM促瘤表型与功能;揭示TAM通过形成局部-系统双向脂质供应维持肿瘤代谢需求,并整合SREBP通路实现动态平衡等机制;以及评述靶向TAM脂质代谢、饮食干预及联合疗法等最新进展;最后进一步提出临床转化方向:基于血浆代谢组学生物标志物、器官特异性代谢差异及空间多组学技术的研究框架等。

     

    Abstract: Lipid metabolism reprogramming in the tumor microenvironment critically drives cancer progression. Tumor-associated macrophages (TAMs), acting as central hubs, promote immunosuppression and metastasis through lipid uptake, processing, and signaling, thereby shaping TAMs' pro-tumor functions. This review systematically examines TAM lipid metabolism mechanisms, focusing on lipid absorption, intracellular handling, and pro-tumorigenic metabolic signaling. It highlights the local-systemic lipid network, revealing TAMs sustain tumor metabolic demands by coordinating bidirectional lipid flux and integrating the SREBP pathway for dynamic balance. Targeted therapeutic strategies, including TAM lipid metabolism inhibitors, dietary interventions, and combination therapies, are reviewed. Finally, clinical translation directions are proposed, emphasizing plasma metabolomic biomarkers, organ-specific metabolic heterogeneity, and spatial multi-omics research frameworks.
     

     

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