Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy?
Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy?
复制标题
对子集进行分类：哪些 T 细胞群介导高效的过继免疫疗法？
DOI：
10.1097/cji.0b013e31827806e6
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Restifo NP
中科院分区：
文献类型：
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作者：
Klebanoff CA;Gattinoni L;Restifo NP
CD8+ T 细胞被描述为幼稚 (TN) 或代表分化和成熟连续体的四种抗原经历亚型之一：干细胞记忆 (TSCM)、中央记忆 (TCM)、效应记忆 (TEM) 和终末分化效应 T 细胞 (TEFF)。在小鼠中，相对于分化程度更高的 TEM 和 TEFF 细胞，分化程度较低的 TN、TSCM 和 TCM 亚群的过继细胞转移 (ACT) 始终表现出优异的体内扩增、持久性和抗肿瘤能力。人类 ACT 试验的回顾性分析证实，低分化 T 细胞亚群的转移与客观临床反应高度相关。这些发现，加上最近通过外源T细胞或嵌合抗原受体的基因工程高效地从头传递抗原反应性的能力，现在对该领域提出了三个重要问题的挑战：1）如何分离低分化的T细胞亚群用于人类临床试验？ 2) 在不破坏年轻亚群的有益特征的情况下，离体扩增 T 细胞的最佳方法是什么？ 3) 是否有必要将年轻的子集与分化程度更高的子集在物理上分开？回答这些问题将有助于合理开发下一代高效且具有潜在治愈性的癌症 T 细胞疗法。
CD8+ T cells have been described as being naïve (TN) or one of four antigen-experienced subtypes representing a continuum of differentiation and maturation: stem cell memory (TSCM), central memory (TCM), effector memory (TEM), and terminally differentiated effector T cells (TEFF). In mice, adoptive cell transfer (ACT) of less differentiated TN, TSCM and TCM subsets have consistently demonstrated superior in vivo expansion, persistence, and antitumor capacities relative to the more differentiated TEM and TEFF cells. Retrospective analyses from human ACT trials have confirmed that transfer of less differentiated T cell subsets is highly correlated with objective clinical responses. These findings, combined with the recent ability to convey de novo antigen reactivity with high efficiency through genetic engineering of exogenous T cell or chimeric antigen receptors, now challenge the field with three important questions: 1) how should less differentiated T cell subsets be isolated for human clinical trials?; 2) what is the best means of expanding T cells ex vivo in such a way as to not corrupt the beneficial traits of the younger subsets?; and 3) is it necessary to physically separate younger subsets from their more differentiated counterparts? Answering these questions will allow for the rational development of the next generation of highly effective and potentially curative T cell therapies for the treatment of cancer.