[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-365747-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-365747-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","reprogrammed-immuno-metabolic-environment-of-cancer-the-driving-force-of-ferroptosis-resistance","Reprogrammed immuno-metabolic environment of cancer - the driving force of ferroptosis resistance","","Ferroptosis is a non-apoptotic, iron-dependent form of cell death driven by metabolism-linked reactive oxygen species, culminating in Fe2+-induced lipid peroxidation. Highly metabolic cancer cells are vulnerable, yet their neoplastic programs rewire metabolism to bypass ferroptosis and generate ferroptosis resistance. Cancer reprogramming also strengthens radical-trapping antioxidant systems and shapes tumor progression. The tumor microenvironment cooperates with tumor metabolism to build an immuno-metabolic niche that sustains proliferation, survival, and therapy-relevant immune regulation.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/reprogrammed-immuno-metabolic-environment-of-cancer-the-driving-force-of-ferroptosis-resistance/365747/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/reprogrammed-immuno-metabolic-environment-of-cancer-the-driving-force-of-ferroptosis-resistance/365747.png","ImageObject",300,407,{"name":42,"@type":43},"Riley West","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why does ferroptosis occur in metabolic cells?","Question",{"text":63,"@type":64},"Ferroptosis results from reactive oxygen species generated during cellular metabolism, which promote Fe2+-driven lipid peroxidation, leading to ferroptotic cell death.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do cancer cells become resistant to ferroptosis?",{"text":68,"@type":64},"Cancer cells reprogram metabolic activities to evade ferroptosis and enhance antioxidant/radical-trapping systems, enabling them to withstand oxidative damage and ferroptotic pressure.",{"name":70,"@type":61,"acceptedAnswer":71},"What role does the tumor microenvironment play in ferroptosis resistance?",{"text":72,"@type":64},"The tumor microenvironment cooperates with tumor metabolism to create an immuno-metabolic environment. 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Molecular Cancer (2025) 24:161 [https://doi.org/10.1186/s12943-025-02337-3](https://doi.org/10.1186/s12943-025-02337-3)  \nMolecular Cancer  \n REVIEW Open Access  \nReprogrammed immuno-metabolic environment of cancer: the driving force of ferroptosis resistance  \nSramana Bhowmick 1, Saptak Banerjee2, Viji Shridhar3 and Susmita Mondal 1*  \nAbstract  \nFerroptosis, the non-apoptotic, iron-dependent form of cell death is an unavoidable outcome and byproduct of cellular metabolism. Reactive oxygen species generation during metabolic activities transcends to Fe2+-induced lipid peroxidation, leading to ferroptosis. Cancer cells being highly metabolic are more prone to ferroptosis. However, their neoplastic nature enables them to bypass ferroptosis and become ferroptosis-resistant. The capability of cancer cells to reprogram its metabolic activities is one of its finest abilities to abort oxidative damage, and hence ferroptosis. Moreover, the reprogrammed metabolism of cancer cells, also associates with the radical trapping antioxidant systems to enhance the scavenging offerroptosis and thereby tumor progression. Additionally, the TME, which is an inevitable part and regulator of carcinogenesis, presents an intricate cooperation with tumor metabolism to build an immuno-metabolic environment to regulate the sustenance of cell proliferation and survival. This review focuses on the current understanding offerroptosis in carcinogenesis and its resistance acquired by cancer cells via several modulators including the radical trapping antioxidant systems, the reprogrammed metabolism, the TME, and intertwined role of cancer metabolism and tumor immunity. The reprogrammed metabolism section further comprehends the functional role of lipids, iron and glucose metabolism against ferroptosis defense separately. The affiliation ofTME in ferroptosis regulation is further sectioned with reference to different immune cells present within the TME such as tumor-associated macrophages, tumor-infiltrating neutrophils, myeloid-derived suppressor cells, T-cells, natural killer cells, dendritic cells, and B-cells, modifying the TME in both pro and anti-tumorigenic manner. Subsequently, this review also discusses the convergence of immuno-metabolic environment in ferroptosis regulation, and eventually brings up research gaps in this context providing consequential and significant questions to explore for better understanding of the immuno-metabolic environment’s role in driving ferroptosis resistance for anti-cancer treatment progress.  \nKeywords Ferroptosis, Ferroptosis resistance, Metabolic reprogramming, Tumor microenvironment, Reprogrammed immune metabolic environment  \n*Correspondence:  \nSusmita Mondal  \n[susmita.dbs@presiuniv.ac.in](susmita.dbs@presiuniv.ac.in)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.or","cbCaipmiXF5RFD8F","https://ap.wps.com/l/cbCaipmiXF5RFD8F","pdf",6590452,22,"English","# Introduction\n## Ferroptosis and cancer cell fate\n## Immuno-metabolic regulation in cancer\n# Core review focus\n## Ferroptosis and its resistance mechanisms\n## Role of reprogrammed metabolism\n## Tumor microenvironment and immune cells\n# Research gaps and outlook","[{\"question\":\"Why does ferroptosis occur in metabolic cells?\",\"answer\":\"Ferroptosis results from reactive oxygen species generated during cellular metabolism, which promote Fe2+-driven lipid peroxidation, leading to ferroptotic cell death.\"},{\"question\":\"How do cancer cells become resistant to ferroptosis?\",\"answer\":\"Cancer cells reprogram metabolic activities to evade ferroptosis and enhance antioxidant/radical-trapping systems, enabling them to withstand oxidative damage and ferroptotic pressure.\"},{\"question\":\"What role does the tumor microenvironment play in ferroptosis resistance?\",\"answer\":\"The tumor microenvironment cooperates with tumor metabolism to create an immuno-metabolic environment. It is shaped by multiple immune cell types and can regulate tumor growth and survival in pro- and anti-tumorigenic ways.\"}]","Reprogrammed immuno-metabolic environment of cancer - the driving force of ferroptosis resistance | PDF",1790162081,55]