Transient-resting culture after activation enhances the generation of CD8+ stem cell-like memory T cells from peripheral blood mononuclear cells

作者：Guangyu Chen, Yuan Long, Yong Zhang, Tiepeng Li, Hongqin You, Lu Han, Peng Qin, Yao Wang, Xue Liu, Jindong Guo, Mengyu Zhang, Kuang Zhang, Lin Li, Peng Yuan, Benling Xu, Quanli Gao · 发表于：Translational Oncology · 年份：2024 · DOI：10.1016/j.tranon.2024.102138 · 被引用次数：3 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、T-cell and B-cell Immunology

• CD8 + T SCM cells differentiate directly from peripheral blood mononuclear cells. • The approach eliminates the step of isolating naïve T cells from PBMCs. • Our findings highlight the dual role of IL-2 in regulating CD8 + T-cell phenotype. • Transient-resting culture after activation is a cost-effective CD8 + T SCM cell generation method. Adoptive cell therapy (ACT) has revolutionized the treatment of patients with cancer. The success of ACT depends largely on transferred T cell status, particularly their less-differentiated state with stem cell-like properties, which enhances ACT effectiveness. Stem cell-like memory T (T SCM ) cells exhibit continuous self-renewal and multilineage differentiation similar to pluripotent stem cells. T SCM cells are promising candidates for cancer immunotherapies, whereas maintenance of a more stem-cell-like state before transfer is challenging. Here, we established a highly efficient protocol for generating CD8 + T SCM cells from peripheral blood mononuclear cells (PBMCs). The process involved activating PBMCs using anti-CD3 monoclonal antibody and RetroNectin, followed by a transient-resting culture period (24 h) and subsequent long-term expansion in vitro with interlukien-2. We report that this transient-resting culture after activation preserves CD8 + T cells in a stem memory phenotype (CD95 + CD45RA + CCR7 + ) compared to the conventional culture method. Further, this approach reduces the expression of T cell immunoglobulin mucin-3, an ...