{"title":"Optimizing mitochondria function in immune cells: implications for cancer immunotherapy.","authors":"Huiyu Li, Wenyi Jin, Junhong Liu, Yundong Zhou, Xiaoli Shan, Yubiao Zhang, Yongliang Kou, Chunyan Deng, Cheng Jin, Junjie Kuang, Yui-Leung Lau, João Conde, Baozhen Huang, Queran Lin","doi":"10.1016/j.trecan.2025.08.006","DOIUrl":null,"url":null,"abstract":"<p><p>The tumor microenvironment (TME) imposes profound metabolic and functional constraints on immune cells, with mitochondrial dysfunction emerging as a pivotal driver of immunosuppression. While mitochondrial metabolism is well recognized for its role in energy production and cellular homeostasis, its dynamic regulation of immune cell activation, differentiation, and exhaustion within the TME remains underexplored. In this review we summarize insights into how TME stressors such as hypoxia, nutrient competition, and metabolic byproducts subvert mitochondrial dynamics, redox balance, and mitochondrial DNA (mtDNA) signaling in T cells, natural killer (NK) cells, and macrophages, thereby directly impairing their antitumor efficacy. We emphasize that the restoration of mitochondrial fitness in immune cells, achieved by targeting metabolites in the TME and mitochondrial quality control, represents a pivotal axis for adoptive cell therapies (ACTs) and TME reprogramming.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":17.5000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.trecan.2025.08.006","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The tumor microenvironment (TME) imposes profound metabolic and functional constraints on immune cells, with mitochondrial dysfunction emerging as a pivotal driver of immunosuppression. While mitochondrial metabolism is well recognized for its role in energy production and cellular homeostasis, its dynamic regulation of immune cell activation, differentiation, and exhaustion within the TME remains underexplored. In this review we summarize insights into how TME stressors such as hypoxia, nutrient competition, and metabolic byproducts subvert mitochondrial dynamics, redox balance, and mitochondrial DNA (mtDNA) signaling in T cells, natural killer (NK) cells, and macrophages, thereby directly impairing their antitumor efficacy. We emphasize that the restoration of mitochondrial fitness in immune cells, achieved by targeting metabolites in the TME and mitochondrial quality control, represents a pivotal axis for adoptive cell therapies (ACTs) and TME reprogramming.
期刊介绍：
Trends in Cancer, a part of the Trends review journals, delivers concise and engaging expert commentary on key research topics and cutting-edge advances in cancer discovery and medicine.
Trends in Cancer serves as a unique platform for multidisciplinary information, fostering discussion and education for scientists, clinicians, policy makers, and patients & advocates.Covering various aspects, it presents opportunities, challenges, and impacts of basic, translational, and clinical findings, industry R&D, technology, innovation, ethics, and cancer policy and funding in an authoritative yet reader-friendly format.
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