Notch 介导的激活 T 细胞向干细胞记忆样 T 细胞的转化及其在过继免疫治疗中的应用。
Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy.
机构信息
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi 2-chome, Fujisawa-shi, Kanagawa 251-8555, Japan.
出版信息
Nat Commun. 2017 May 22;8:15338. doi: 10.1038/ncomms15338.
Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (T) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8 T cells can be generated in vitro from naive CD8 T cells via Wnt signalling; however, methods do not yet exist for inducing T cells from activated or memory T cells. Here, we show a strategy for generating T-like cells in vitro (iT cells) from activated CD4 and CD8 T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iT cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.
过继性 T 细胞免疫疗法是一种很有前途的癌症治疗方法。干细胞记忆 T（T）细胞被认为是一类具有长寿命和高增殖能力的记忆 T 细胞。CD8 T 细胞可以通过 Wnt 信号从幼稚 CD8 T 细胞体外产生，但是，目前还没有从激活或记忆 T 细胞诱导 T 细胞的方法。在这里，我们展示了一种在体外从激活的 CD4 和 CD8 T 细胞（iT 细胞）中生成 T 样细胞的策略，该方法通过与表达 Notch 配体的基质细胞共培养来实现。iT 细胞丧失 PD-1 和 CTLA-4 的表达，并在重新刺激后产生大量的肿瘤特异性效应细胞。因此，该方法可用于生成用于过继免疫治疗的抗原特异性效应 T 细胞。
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