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结直肠癌中的代谢-免疫轴:通过代谢物信号重塑肿瘤微环境

英文原题:The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling.

查看英文原题

The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling.

PubMed 2025/12/19(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

代谢重编程是肿瘤的一个决定性标志,通过重塑核心生物能量和生物合成途径,在维持恶性生长中发挥关键作用。除了支持肿瘤细胞增殖、存活和转移外,它还通过营养竞争、免疫抑制性代谢物积累以及免疫细胞功能调节,深刻塑造肿瘤微环境,从而促进免疫逃逸和治疗耐药。本综述全面阐述了结直肠癌中的代谢重编程,涵盖葡萄糖代谢(Warburg效应)、三羧酸循环重塑、脂质生物合成/氧化、胆固醇代谢以及氨基酸(谷氨酰胺、甲硫氨酸、色氨酸、精氨酸)代谢的关键改变。

进一步剖析了这些代谢转变如何影响结直肠癌的肿瘤微环境,包括其对效应免疫细胞(CD8 + T细胞、NK细胞)、免疫抑制性群体(Tregs、MDSCs、M2-TAMs)和抗原呈递细胞的影响。

此外,本综述强调了肠道微生物群及其代谢物(如SCFAs、次级胆汁酸和吲哚类)通过代谢串扰重塑免疫微环境的作用。总体而言,本工作提供了对CRC代谢重编程及其微环境影响的全面的理解,为指导CRC新型代谢靶向治疗策略的开发提供了关键见解。

展开英文摘要原文

Metabolic reprogramming is a defining hallmark of tumors, and plays a pivotal role in sustaining malignant growth by rewiring core bioenergetic and biosynthetic pathways. Beyond supporting tumor cell proliferation, survival, and metastasis, it profoundly shapes the tumor microenvironment through nutrient competition, accumulation of immunosuppressive metabolites, and modulation of immune cell function, thereby facilitating immune evasion and therapy resistance.

This review comprehensively elaborates on metabolic reprogramming in colorectal cancer, covering key alterations in glucose metabolism (Warburg effect), tricarboxylic acid cycle remodeling, lipid biosynthesis/oxidation, cholesterol metabolism, and amino acid (glutamine, methionine, tryptophan, arginine) metabolism.

It further dissects how these metabolic shifts impact the tumor microenvironment in colorectal cancer, including their effects on effector immune cells (CD8 + T cells, NK cells), immunosuppressive populations (Tregs, MDSCs, M2-TAMs), and antigen-presenting cells.

Additionally, this review highlights the role of the gut microbiota and their metabolites (e. g. , SCFAs, secondary bile acids and indoles) in remodeling the immune microenvironment via metabolic crosstalk.

Overall, this work provides a comprehensive understanding of CRC metabolic reprogramming and its microenvironmental impacts, offering critical insights to guide the development of novel metabolism-targeted therapeutic strategies for CRC.

论文信息

作者
Hu S、Heng H、Yang F、Wang M、Liu G、Xiang Y、Miao H
第一作者单位
Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing, China.China
通讯作者单位
Jinfeng Laboratory, Chongqing, China.China
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 41488637 · DOI 10.3389/fimmu.2025.1735873