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

作者：Mengshi Luo, Wenjian Gong, Yuewen Zhang, Huayi Li, Ding Ma, Kongming Wu, Qinglei Gao, Yong Fang · 发表于：Cell Communication and Signaling · 年份：2023 · DOI：10.1186/s12964-023-01354-3 · 被引用次数：17 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、CRISPR and Genetic Engineering

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 (T SCM ) 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 T SCM cell induction regulators and acquire more T SCM 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 T SCM 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 ...