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

Sep 28, 2026

Uploaded by Callum

Metabolic reprogramming is a defining hallmark of tumors, sustaining malignant growth by rewiring bioenergetic and biosynthetic pathways and reshaping the tumor microenvironment. In colorectal cancer, metabolic changes promote immune evasion and resistance to therapy through nutrient competition and accumulation of immunosuppressive metabolites that alter immune-cell function. This review details CRC metabolic remodeling across glucose, TCA cycle, lipid, cholesterol, and amino-acid pathways, and explains how these shifts affect effector cells, immunosuppressive populations, antigen-presenting cells, and gut-microbiota–derived metabolites via metabolic crosstalk, informing metabolism-targeted strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages32

Reading Time1 h 21 min

AccessFree to download

Background

Epidemiology and risk factors

Metabolic reprogramming in colorectal cancer

Core metabolic adaptations

Metabolism-driven remodeling of the tumor microenvironment

Effects on immune and antigen-presenting cells

Gut microbiota metabolites and metabolic crosstalk

TYPE Review PUBLISHED 19 December 2025 DOI 10.3389/fimmu.2025.1735873 OPEN ACCESS EDITED BY Paulo Rodrigues-Santos, University of Coimbra, Portugal REVIEWED BY Bjørn Steen Skålhegg, University of Oslo, Norway Ming Yi, Zhejiang University, China *CORRESPONDENCE Guoxiang Liu [Liuguoxiang927@126.com](Liuguoxiang927@126.com)[ ](Liuguoxiang927@126.com)Yuancai Xiang [yuancaix@swmu.edu.cn](yuancaix@swmu.edu.cn)[ ](yuancaix@swmu.edu.cn)Hongming Miao [hongmingmiao@sina.com](hongmingmiao@sina.com) RECEIVED 30 October 2025 REVISED 14 November 2025 ACCEPTED 17 November 2025 PUBLISHED 19 December 2025 CITATION Hu S, Heng H, Yang F, Wang M, Liu G, Xiang Y and Miao H (2025) The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling. Front. Immunol. 16:1735873 . doi: 10.3389/fimmu.2025.1735873 COPYRIGHT © 2025 Hu, Heng, Yang, Wang, Liu, Xiang and Miao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling Shaofan Hu 1,2,3, Hui Heng 3, Fang Yang 3,4,5,6, Meng Wang 3,4,6, Guoxiang Liu 1*, Yuancai Xiang 7* and Hongming Miao 3,4,6* 1Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing, China, 2College of Bioengineering, Chongqing University, Chongqing, China, 3Jinfeng Laboratory, Chongqing, China, 4 Department of Pathophysiology, College of High Altitude Military Medicine, Third Military Medical University (Army Medical University), Chongqing, China, 5 Department of Physiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China, 6 Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Third Military Medical University (Army Medical University), Chongqing, China, 7 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China 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 antigenpresenting 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. KEYWORDS colorectal cancer (CRC), metabolic reprogramming,

FAQs

Why is metabolic reprogramming important in colorectal cancer?

It rewires bioenergetic and biosynthetic pathways to support tumor proliferation and survival, while also reshaping the tumor microenvironment and contributing to immune evasion and therapy resistance.

Which metabolic pathways does the review cover for CRC?

It addresses alterations in glucose metabolism (including the Warburg effect), TCA cycle remodeling, lipid biosynthesis/oxidation, cholesterol metabolism, and amino-acid metabolism such as glutamine, methionine, tryptophan, and arginine.

How do metabolic changes affect immune cells in the CRC tumor microenvironment?

Metabolic shifts influence effector immune cells (e.g., CD8+ T cells and NK cells), immunosuppressive populations (e.g., Tregs, MDSCs, and M2-TAMs), and antigen-presenting cells.

What role do gut microbiota and their metabolites play?

The review highlights how gut microbiota metabolites, including SCFAs, secondary bile acids, and indoles, remodel the immune microenvironment through metabolic crosstalk.

Sep 28, 2026

Uploaded by Callum