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New insights into the stemness of adoptively transferred T cells by gammac family cytokines.

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单位: [1]Department of Gynecological Oncology,Tongji Hospital,Tongji MedicalCollege,Huazhong University of Science and Technology,Wuhan,China [2]National Clinical Research Center for Obstetrics and Gynecology,CancerBiology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Scienceand Technology,Wuhan,China [3]Department of Oncology,Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China
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关键词: Stemness Stem cell-like memory T cells (TSCM) Adoptive cell therapy (ACT) γc family cytokines

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T cell-based adoptive cell therapy (ACT) has exhibited excellent antitumoral efficacy exemplified by the clinical breakthrough of chimeric antigen receptor therapy (CAR-T) in hematologic malignancies. It relies on the pool of functional T cells to retain the developmental potential to serially kill targeted cells. However, failure in the continuous supply and persistence of functional T cells has been recognized as a critical barrier to sustainable responses. Conferring stemness on infused T cells, yielding stem cell-like memory T cells (TSCM) characterized by constant self-renewal and multilineage differentiation similar to pluripotent stem cells, is indeed necessary and promising for enhancing T cell function and sustaining antitumor immunity. Therefore, it is crucial to identify TSCM cell induction regulators and acquire more TSCM cells as resource cells during production and after infusion to improve antitumoral efficacy. Recently, four common cytokine receptor γ chain (γc) family cytokines, encompassing interleukin-2 (IL-2), IL-7, IL-15, and IL-21, have been widely used in the development of long-lived adoptively transferred TSCM in vitro. However, challenges, including their non-specific toxicities and off-target effects, have led to substantial efforts for the development of engineered versions to unleash their full potential in the induction and maintenance of T cell stemness in ACT. In this review, we summarize the roles of the four γc family cytokines in the orchestration of adoptively transferred T cell stemness, introduce their engineered versions that modulate TSCM cell formation and demonstrate the potential of their various combinations. Video Abstract.© 2023. The Author(s).

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出版当年[2022]版:
大类 | 2 区 生物学
小类 | 2 区 细胞生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 2 区 细胞生物学
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出版当年[2021]版:
Q2 CELL BIOLOGY
最新[2023]版:
Q1 CELL BIOLOGY

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第一作者单位: [1]Department of Gynecological Oncology,Tongji Hospital,Tongji MedicalCollege,Huazhong University of Science and Technology,Wuhan,China [2]National Clinical Research Center for Obstetrics and Gynecology,CancerBiology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Scienceand Technology,Wuhan,China
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通讯机构: [1]Department of Gynecological Oncology,Tongji Hospital,Tongji MedicalCollege,Huazhong University of Science and Technology,Wuhan,China [2]National Clinical Research Center for Obstetrics and Gynecology,CancerBiology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Scienceand Technology,Wuhan,China
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