Development and characterization of naive single-type tumor antigen-specific CD8+ T lymphocytes from murine pluripotent stem cells.
Development and characterization of naive single-type tumor antigen-specific CD8+ T lymphocytes from murine pluripotent stem cells.
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来自鼠多能干细胞的幼稚单型肿瘤抗原特异性 CD8 T 淋巴细胞的开发和表征。
DOI：
10.1080/2162402x.2017.1334027
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发表时间：
2017
期刊：
影响因子：
7.2
通讯作者：
Song,Jianxun
中科院分区：
文献类型：
--
作者：
Lei,Fengyang;Haque,Mohammad;Sandhu,Praneet;Ravi,Swetha;Song,Jianyong;Ni,Bing;Zheng,Songguo;Fang,Deyu;Jia,Hongyan;Yang,Jin-Ming;Song,Jianxun
区分肿瘤抗原特异性细胞毒性T淋巴细胞（CTL）与多能干细胞（PSC）的最佳方法仍然难以捉摸。在目前的研究中，我们发现通过Notch配体的体外引发和体内发育的结合促进了肿瘤Ag特异性CTL的产生，有效地抑制了肿瘤的生长。我们将用酪氨酸酶相关蛋白2（TRP 2）特异性T细胞受体遗传修饰的鼠诱导的PSC（iPSC）与表达Notch配体Delta样1和4（OP 9-DL 1/DL 4）的OP 9细胞系共培养一周，然后过继转移到受体C67 BL/6小鼠中。三周后，皮下接种B16黑素瘤细胞，并评估iPSC衍生的T细胞的抗肿瘤活性。我们观察到TRP 2特异性iPSC-CD 8 +T细胞的发育，其响应于Ag刺激并浸润到黑素瘤组织中，显著抑制肿瘤生长，并提高荷瘤小鼠的存活率。因此，这种方法可能为恶性肿瘤的治疗提供一种新的有效策略。
Optimal approaches to differentiate tumor antigen-specific cytotoxic T lymphocytes (CTLs) from pluripotent stem cells (PSCs) remain elusive. In the current study, we showed that combination ofin vitropriming through Notch ligands andin vivodevelopment facilitated the generation of tumor Ag-specific CTLs that effectively inhibited tumor growth. We co-cultured the murine induced PSCs (iPSCs) genetically modified with tyrosinase-related protein 2 (TRP2)-specific T cell receptors with OP9 cell line expressing both Notch ligands Delta-like 1 and 4 (OP9-DL1/DL4) for a week before adoptively transferred into recipient C67BL/6 mice. Three weeks later, B16 melanoma cells were inoculated subcutaneously, and the antitumor activity of the iPSC-derived T cells was assessed. We observed the development of the TRP2-specific iPSC-CD8+T cells that responded to Ag stimulation and infiltrated into melanoma tissues, significantly inhibited the tumor growth, and improved the survival of the tumor-bearing mice. Thus, this approach may provide a novel effective strategy to treatment of malignant tumors.