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肿瘤中免疫抑制细胞的代谢适应:机制与治疗靶点

英文原题:Metabolic adaptations of immunosuppressive cells in cancer: mechanisms and therapeutic targets.

PubMed 2026/05/07(内容时间) Exp Mol Med Q1 · IF 17.5(JCR 2025)

研究概要

肿瘤微环境中存在多种免疫抑制细胞群,包括调节性T细胞、髓源性抑制细胞、肿瘤相关巨噬细胞及其他耐受性亚群,这些细胞驱动免疫逃逸和治疗耐药。

中文摘要

肿瘤微环境中存在多种免疫抑制细胞群体,包括调节性T细胞、髓源性抑制细胞、肿瘤相关巨噬细胞及其他耐受性亚群,这些细胞驱动免疫逃逸和治疗耐药。这些细胞经过代谢重编程,以维持其抑制功能并在缺氧、营养剥夺和氧化应激条件下存活。重要的是,它们的代谢活动不仅支持自身适应性,还通过消耗必需营养物、产生抑制性代谢物和改变信号阈值,营造出拮抗效应T细胞和NK 细胞的不利环境。这种免疫代谢竞争加剧了免疫功能障碍,并限制了检查点阻断和过继细胞疗法的疗效。在此,我们描述了TME内的免疫抑制细胞类型、其关键代谢适应以及它们抑制抗肿瘤免疫的机制。最后,我们讨论了旨在破坏这些代谢程序以重塑TME并提高当前和下一代免疫疗法成功率的治疗策略。总体而言,理解抑制性免疫细胞与效应免疫细胞之间的代谢串扰,将为设计精准代谢干预和改善癌症免疫治疗的持久应答提供新机会。

展开英文摘要原文

The tumor microenvironment harbors diverse immunosuppressive cell populations-including regulatory T cells, myeloid-derived suppressor cells, tumor-associated macrophages and other tolerogenic subsets-that drive immune evasion and therapeutic resistance. These cells are metabolically reprogrammed to sustain their suppressive function and survive under conditions of hypoxia, nutrient deprivation and oxidative stress. Importantly, their metabolic activity not only supports their own fitness but also creates a hostile environment that antagonizes effector T and natural killer cells by depleting essential nutrients, generating inhibitory metabolites, and altering signaling thresholds. This immunometabolic competition reinforces immune dysfunction and limits the efficacy of checkpoint blockade and adoptive cell therapies. Here we delineate the immunosuppressive cell types within the TME, their key metabolic adaptations and the mechanisms by which they suppress antitumor immunity. Finally, we discuss therapeutic strategies aimed at disrupting these metabolic programs to remodel the TME and enhance the success of current and next-generation immunotherapies. Collectively, understanding the metabolic crosstalk between suppressive and effector immune cells will provide new opportunities to design precision metabolic interventions and improve durable responses to cancer immunotherapy.

论文信息

作者
Kim J、Shin JM、Um Y、Yuan S、Lim SA
第一作者单位
Department of Life Science, Ewha Womans University, Seoul, Republic of Korea.South Korea
通讯作者单位
Department of Life Science, Ewha Womans University, Seoul, Republic of Korea. seonlim@ewha.ac.kr.South Korea
文献类型
综述
期刊
Experimental & molecular medicine2026 May
原文标识
PubMed 42091642 · DOI 10.1038/s12276-026-01713-3