文章：

通向干细胞之路：构建终极抗肿瘤T细胞

Paths to stemness: building the ultimate antitumour T cell

原文发布日期：2012-09-21

DOI: 10.1038/nrc3322

类型: Review Article

开放获取: 否

要点：

1. T lymphocytes transition through progressive stages of differentiation that are characterized by a stepwise loss of functional and therapeutic potential.
2. Subsets of mature T cells exhibit the stem cell-like attributes of self-renewal, multipotency and the ability to undergo asymmetric division.
3. Evolutionarily conserved pathways regulating stemness are active in T cells, including T memory stem cells, T helper 17 cells and interleukin-17 (IL-17)-producing CD8⁺ T cells.
4. Pharmacological and genetic induction of stem cell pathways can be used to generate tumour-specific T cells with stem cell-like properties.
5. Reprogramming terminally differentiated tumour-reactive T cells to display naive or stem cell-like functionalities might be obtained through the expression of transcription factors or microRNAs that are associated with naive or T memory stem cells.
6. Stem cell-like T cells possess enhanced capacities to engraft, persist and mediate prolonged immune attack against tumour masses that are sustained by long-lived cancer stem cells.

要点翻译：

1. T淋巴细胞经历渐进的分化阶段，其特点是逐步丧失功能性和治疗潜力。
2. 成熟T细胞亚群表现出干细胞样特性，包括自我更新、多能性和进行不对称分裂的能力。
3. 进化上保守的干性调控通路在T细胞中活跃存在，涵盖T记忆干细胞、辅助性T17细胞以及产生白细胞介素17（IL-17）的CD8+ T细胞。
4. 通过药理学和遗传学方法诱导干细胞通路可生成具有干细胞样特性的肿瘤特异性T细胞。
5. 通过表达与初始T细胞或T记忆干细胞相关的转录因子或微小RNA，可能重编程终末分化的肿瘤反应性T细胞，使其呈现初始或干细胞样功能。
6. 具有干细胞样特性的T细胞具有更强的定植能力、持久存续能力，并能对由长寿癌症干细胞维持的肿瘤团块介导长期免疫攻击。

英文摘要：

Stem cells are defined by the ability to self-renew and to generate differentiated progeny, qualities that are maintained by evolutionarily conserved pathways that can lead to cancer when deregulated. There is now evidence that these stem cell-like attributes and signalling pathways are also shared among subsets of mature memory T lymphocytes. We discuss how using stem cell-like T cells can overcome the limitations of current adoptive T cell therapies, including inefficient T cell engraftment, persistence and ability to mediate prolonged immune attack. Conferring stemness to antitumour T cells might unleash the full potential of cellular therapies.

摘要翻译： 

干细胞被定义为能够自我更新并产生分化子代的能力，这些特性由进化上保守的信号通路维持，一旦失调便可能导致癌症。现有证据表明，这些干细胞样特征及其信号通路同样存在于部分成熟记忆T淋巴细胞亚群中。我们探讨了如何利用干细胞样T细胞克服当前过继性T细胞疗法的局限，包括T细胞植入效率低、持久性差以及介导长期免疫攻击能力不足等问题。赋予抗肿瘤T细胞“干性”特性，有望充分释放细胞疗法的潜能。

原文链接：

Paths to stemness: building the ultimate antitumour T cell