{"title":"Reprogramming T cell stemness against cancer.","authors":"Jiaqi Wang, Ruochen Yan, Dingjiacheng Jia, Shujie Chen","doi":"10.1016/j.trecan.2025.09.004","DOIUrl":null,"url":null,"abstract":"<p><p>Stem-like CD8<sup>+</sup> T cells - characterized by high-level expression of the transcription factor TCF-1, and known as progenitor exhausted T (T<sub>pex</sub>) cells - have emerged as crucial mediators of durable antitumor immunity. These cells demonstrate unique self-renewal capacity, multipotency, and enhanced responsiveness to immune checkpoint blockade therapy. This review synthesizes current understanding of T<sub>pex</sub> cell biology, including their defining characteristics, tissue distribution, and functional importance in antitumor immunity. We focus particularly on innovative approaches to preserve and enhance T cell stemness through combination therapies, cytokine signal modulation, epigenetic regulation, tumor microenvironment modification, and microbiota-based interventions. The development of these next-generation immunotherapies targeting T cell stemness represents a transformative frontier in oncology, holding significant promise for improving therapeutic outcomes in cancer patients.</p>","PeriodicalId":23336,"journal":{"name":"Trends in cancer","volume":" ","pages":""},"PeriodicalIF":17.5000,"publicationDate":"2025-10-02","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.2025.09.004","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
Stem-like CD8+ T cells - characterized by high-level expression of the transcription factor TCF-1, and known as progenitor exhausted T (Tpex) cells - have emerged as crucial mediators of durable antitumor immunity. These cells demonstrate unique self-renewal capacity, multipotency, and enhanced responsiveness to immune checkpoint blockade therapy. This review synthesizes current understanding of Tpex cell biology, including their defining characteristics, tissue distribution, and functional importance in antitumor immunity. We focus particularly on innovative approaches to preserve and enhance T cell stemness through combination therapies, cytokine signal modulation, epigenetic regulation, tumor microenvironment modification, and microbiota-based interventions. The development of these next-generation immunotherapies targeting T cell stemness represents a transformative frontier in oncology, holding significant promise for improving therapeutic outcomes in cancer patients.
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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