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肿瘤免疫中的胆固醇代谢:机制与癌症治疗机遇

英文原题:Cholesterol metabolism in tumor immunity: Mechanisms and therapeutic opportunities for cancer.

查看英文原题

Cholesterol metabolism in tumor immunity: Mechanisms and therapeutic opportunities for cancer.

PubMed 2025/02/13(内容时间) Biochem Pharmacol Q1 · IF 6.5(JCR 2025)

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中文摘要

胆固醇是细胞膜的重要组成成分,在免疫细胞和肿瘤细胞的生存中发挥关键作用。肿瘤细胞和免疫细胞中胆固醇代谢的重编程可影响肿瘤进展和抗肿瘤免疫应答。靶向调节胆固醇代谢的策略已被证明可有效抑制肿瘤生长并增强抗肿瘤免疫功能。本综述对细胞内胆固醇稳态调控进行了全面分析,重点关注关键基因和信号通路。特别强调了胆固醇存在状态(酯化/游离)、胆固醇水平及其代谢产物在免疫细胞和肿瘤细胞中的调控机制和重要性。

此外,本综述深入探讨了肿瘤微环境(TME)中胆固醇代谢及来源(内源性/外源性)如何促进肿瘤细胞、免疫抑制细胞和免疫效应细胞之间的相互作用,从而推动癌症进展和免疫逃逸。

同时深入探讨了目前关于胆固醇代谢产物及相关药物在调控肿瘤发展或免疫治疗中作用的认识。最后,概述了靶向胆固醇代谢治疗及联合治疗在癌症管理中疗效的临床和临床前试验的最新进展,并提出了肿瘤免疫领域潜在的未来研究方向。本综述有望为以胆固醇代谢调控为中心的癌症免疫治疗潜力研究提供新的视角和途径。

展开英文摘要原文

Cholesterol is an essential component of the cell membrane which plays a critical role in the survival of immune and tumor cells. Reprogramming of cholesterol metabolism in both tumor cells and immune cells can impact tumor progression and anti-tumor immune responses. Strategies aimed at modulating cholesterol metabolism have been demonstrated to be effective in hindering tumor growth and boosting anti-tumor immune functions.

This review provides a thorough analysis of intracellular cholesterol homeostasis regulation in cells, focusing on key genes and signaling pathways. It particularly emphasizes the regulatory mechanisms and importance of the cholesterol presence state (esterified/free), levels of cholesterol, and its metabolites in immune and tumor cells.

Additionally, the review thoroughly explores how cholesterol metabolism and sources (endogenous/exogenous) in the tumor microenvironment (TME) contribute to the interplay among tumor cells, immune suppressor cells, and immune effector cells, promoting cancer progression and immune evasion. It also delves into current insights on the influence of cholesterol metabolites and related drugs in regulating tumor development or immunotherapy.

Finally, it presents an overview of recent advancements in clinical and preclinical trials investigating the efficacy of targeted cholesterol metabolism treatments and combination therapies in cancer management, while proposing potential future research directions in tumor immunity. This review is poised to offer fresh perspectives and avenues for examining the potential of cancer immunotherapy centered on cholesterol metabolism regulation.

论文信息

作者
Guo XJ、Zhu BB、Li J、Guo P、Niu YB、Shi JL、Yokoyama W、Huang QS
第一作者单位
Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi West Road, Xi'an, Shaanxi 710072, PR China.China
通讯作者单位
Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi West Road, Xi'an, Shaanxi 710072, PR China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, No. 45th, Gaoxin South 9th Road, Nanshan District, Shenzhen City 518063, PR China. Electronic address: shaoyan@nwpu.edu.cn.China
文献类型
综述 · 非美国政府资助研究
期刊
Biochemical pharmacology2025 Apr
原文标识
PubMed 39954742 · DOI 10.1016/j.bcp.2025.116802