γc 家族细胞因子作用下过继转移 T 细胞干性的新见解

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 chain ( c) 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 c family cytokines in the orchestration of adoptively transferred T cell stemness, introduce their engineered versions that modulate T SCM cell formation and demonstrate the potential of their various combinations. Video Abstract.