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These coordinated shifts generate an immunosuppressive niche that drives tumor progression and therapeutic resistance while regulating immunotherapy performance. Multi-omics approaches, including metabolomics, proteomics, single-cell sequencing, and spatial omics, enable immune–metabolism signature mapping, predictive biomarker discovery, and identification of therapeutic vulnerabilities. Combining metabolic inhibitors with checkpoint blockade and modulating amino-acid metabolism offers strategies to overcome resistance and support precision immunotherapy translation.",{"@graph":69,"@context":122},[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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/metabolic-reprogramming-in-the-postmetastatic-tumor-microenvironment-multi-omics-insights-into-determinants-of-immunotherapy-response/346271/",{"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/metabolic-reprogramming-in-the-postmetastatic-tumor-microenvironment-multi-omics-insights-into-determinants-of-immunotherapy-response/346271.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does metabolic reprogramming influence the post-metastatic tumor immune microenvironment (TIME)?","Question",{"text":112,"@type":113},"It alters glycolysis, lipid metabolism, and metal-dependent cell death pathways and coordinates these changes with the tryptophan–IDO1–kynurenine axis, collectively forming an immunosuppressive niche that supports progression and resistance.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which metabolic features are highlighted as contributors to immunotherapy resistance?",{"text":117,"@type":113},"The document emphasizes changes in glycolysis and lactate accumulation, lipid metabolic rewiring, ferroptosis/cuproptosis-linked metal-dependent death pathways, and the tryptophan–IDO1–kynurenine axis.",{"name":119,"@type":110,"acceptedAnswer":120},"How do multi-omics technologies help connect metabolism to immune regulation?",{"text":121,"@type":113},"They provide high-resolution metabolomic, proteomic, single-cell, and spatial data to decode immune–metabolic interactions, identify predictive biomarkers, and reveal metabolic–immune signatures and therapeutic vulnerabilities.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},346271,1790193346,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","TYPE Review  \nPUBLISHED 05 January 2026  \nDOI 10.3389/fimmu.2025.1742855  \nOPEN ACCESS  \nEDITED BY  \nHailin Tang,  \nSun Yat-sen University Cancer Center (SYSUCC), China  \nREVIEWED BY  \nHengrui Liu,  \nUniversity of Cambridge, United Kingdom Qinghua Yin,  \nYueyang Central Hospital, China Yuanyin Teng,  \nZhejiang University, China  \n*CORRESPONDENCE  \nYuxi Dongye  \n [dongyeyuxi@163.com](dongyeyuxi@163.com)[ ](dongyeyuxi@163.com)Zhenwang Zhang  \n [zhenwangzhang@hbust.edu.cn](zhenwangzhang@hbust.edu.cn)  \n†These authors have contributed equally to this work  \nRECEIVED 09 November 2025  \nREVISED 06 December 2025  \nACCEPTED 10 December 2025  \nPUBLISHED 05 January 2026  \nCITATION  \nLi M, Wang T, Zhang Z and Dongye Y (2026) Metabolic reprogramming in the postmetastatic tumor microenvironment: multiomics insights into determinants of immunotherapy response.  \nFront. Immunol. 16:1742855 .  \ndoi: 10.3389/fimmu.2025.1742855  \nCOPYRIGHT  \n© 2026 Li, Wang, Zhang and Dongye. This isan 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.  \nMetabolic reprogramming in the post-metastatic tumor microenvironment: multi-omics insights into determinants of immunotherapy response  \nMengxi Li 1†, Tingting Wang 2,3†, Zhenwang Zhang 1* and Yuxi Dongye 4*  \n1School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning, Hubei, China, 2 Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, China, 3 Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China, 4 Department of Breast Surgery, Jinan Third People’s Hospital, Jinan, Shandong, China  \nMetabolic reprogramming has emerged as a central determinant of immune modulation in the post-metastatic tumor immune microenvironment (TIME) . Alterations in glycolysis and lactate accumulation, lipid metabolic rewiring, metal-dependent cell death pathways such as ferroptosis and cuproptosis, and the tryptophan–IDO1–kynurenine axis collectively contribute to an immunosuppressive niche that drives tumor progression and therapeutic resistance. These metabolic shifts are not isolated events but are intricately connected with immune-regulatory networks, profoundly influencing the efficacy of immunotherapy. Advances in multi-omics technologies—including metabolomics, proteomics, single-cell sequencing, and spatial omics—have provided unprecedented resolution to decode these complex interactions, enabling the identification of predictive biomarkers, delineation of metabolic– immune signatures, and discovery of therapeutic vulnerabilities. Integrating these multi-layered datasets has paved the way for precision medicine strategies that tailor immunotherapy to patient-specific metabolic and immune contexts. Therapeutically, combining metabolic inhibitors with immune checkpoint blockade, exploiting ferroptosis or cuproptosis to enhance tumor immunogenicity, or modulating amino acid metabolism to reverse immune tolerance are promising strategies to overcome resistance and expand patient benefit. Looking forward, the integration of multi-omics-guided biomarkers, AI-driven analytics, and advanced delivery systems such as nanoparticles and engineered exosomes will accelerate the translation of these insights into clinical practice. Decoding the metabolism–immunity crosstalk through multi-omics  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nnot only advances our understanding of metastatic cancer biology but also paves the way f","cbCairukuQ5moxsb","https://ap.wps.com/l/cbCairukuQ5moxsb","pdf",2316316,22,"English","# Introduction\n## Metabolism–immunity crosstalk in oncology\n## Post-metastatic TIME and immunosuppressive rewiring","[{\"question\":\"How does metabolic reprogramming influence the post-metastatic tumor immune microenvironment (TIME)?\",\"answer\":\"It alters glycolysis, lipid metabolism, and metal-dependent cell death pathways and coordinates these changes with the tryptophan–IDO1–kynurenine axis, collectively forming an immunosuppressive niche that supports progression and resistance.\"},{\"question\":\"Which metabolic features are highlighted as contributors to immunotherapy resistance?\",\"answer\":\"The document emphasizes changes in glycolysis and lactate accumulation, lipid metabolic rewiring, ferroptosis/cuproptosis-linked metal-dependent death pathways, and the tryptophan–IDO1–kynurenine axis.\"},{\"question\":\"How do multi-omics technologies help connect metabolism to immune regulation?\",\"answer\":\"They provide high-resolution metabolomic, proteomic, single-cell, and spatial data to decode immune–metabolic interactions, identify predictive biomarkers, and reveal metabolic–immune signatures and therapeutic vulnerabilities.\"}]","Metabolic reprogramming in the postmetastatic tumor microenvironment - multi-omics insights into determinants of immunotherapy response | PDF",1790060746,55]