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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.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-metabolism-immune-axis-in-colorectal-cancer-remodeling-the-tumor-microenvironment-through-metabolite-signaling-review/415168/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-metabolism-immune-axis-in-colorectal-cancer-remodeling-the-tumor-microenvironment-through-metabolite-signaling-review/415168.png","ImageObject",300,407,{"name":92,"@type":93},"\tCallum ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-08","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"Why is metabolic reprogramming important in colorectal cancer?","Question",{"text":112,"@type":113},"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.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which metabolic pathways does the review cover for CRC?",{"text":117,"@type":113},"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.",{"name":119,"@type":110,"acceptedAnswer":120},"How do metabolic changes affect immune cells in the CRC tumor microenvironment?",{"text":121,"@type":113},"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.",{"name":123,"@type":110,"acceptedAnswer":124},"What role do gut microbiota and their metabolites play?",{"text":125,"@type":113},"The review highlights how gut microbiota metabolites, including SCFAs, secondary bile acids, and indoles, remodel the immune microenvironment through metabolic crosstalk.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},415168,1791165825,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149,"preview_page_count":4},137451211410,"https://ap-avatar.wpscdn.com/avatar/2000bb0a9246f588df?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786362646172706240","TYPE Review  \nPUBLISHED 19 December 2025 DOI 10.3389/fimmu.2025.1735873  \nOPEN ACCESS  \nEDITED BY  \nPaulo Rodrigues-Santos,  \nUniversity of Coimbra, Portugal  \nREVIEWED BY  \nBjørn Steen Skålhegg, University of Oslo, Norway Ming Yi,  \nZhejiang University, China  \n*CORRESPONDENCE  \nGuoxiang Liu  \n [Liuguoxiang927@126.com](Liuguoxiang927@126.com)[ ](Liuguoxiang927@126.com)Yuancai Xiang  \n[yuancaix@swmu.edu.cn](yuancaix@swmu.edu.cn)[ ](yuancaix@swmu.edu.cn)Hongming Miao  \n [hongmingmiao@sina.com](hongmingmiao@sina.com)  \nRECEIVED 30 October 2025  \nREVISED 14 November 2025  \nACCEPTED 17 November 2025  \nPUBLISHED 19 December 2025  \nCITATION  \nHu S, Heng H, Yang F, Wang M, Liu G, Xiang Y and Miao H (2025) The metabolism-immune  \naxis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling.  \nFront. Immunol. 16:1735873 .  \ndoi: 10.3389/fimmu.2025.1735873  \nCOPYRIGHT  \n© 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.  \nThe metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling  \nShaofan 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*  \n1Center 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,  \nSichuan, China  \nMetabolic 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.  \nKEYWORDS  \ncolorectal cancer (CRC), metabolic reprogramming, ","cbCaieVM44fMyS1I","https://ap.wps.com/l/cbCaieVM44fMyS1I","pdf",1875609,32,"English","# Background\n## Epidemiology and risk factors\n# Metabolic reprogramming in colorectal cancer\n## Core metabolic adaptations\n# Metabolism-driven remodeling of the tumor microenvironment\n## Effects on immune and antigen-presenting cells\n# Gut microbiota metabolites and metabolic crosstalk","[{\"question\":\"Why is metabolic reprogramming important in colorectal cancer?\",\"answer\":\"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.\"},{\"question\":\"Which metabolic pathways does the review cover for CRC?\",\"answer\":\"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.\"},{\"question\":\"How do metabolic changes affect immune cells in the CRC tumor microenvironment?\",\"answer\":\"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.\"},{\"question\":\"What role do gut microbiota and their metabolites play?\",\"answer\":\"The review highlights how gut microbiota metabolites, including SCFAs, secondary bile acids, and indoles, remodel the immune microenvironment through metabolic crosstalk.\"}]","The metabolism-immune axis in colorectal cancer - remodeling the tumor microenvironment through metabolite signaling - review | PDF",1790600305,81]