Autor: |
Mengshi Luo, Wenjian Gong, Yuewen Zhang, Huayi Li, Ding Ma, Kongming Wu, Qinglei Gao, Yong Fang |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Cell Communication and Signaling, Vol 21, Iss 1, Pp 1-23 (2023) |
Druh dokumentu: |
article |
ISSN: |
1478-811X |
DOI: |
10.1186/s12964-023-01354-3 |
Popis: |
Abstract 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 |
Databáze: |
Directory of Open Access Journals |
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