Precursor exhausted T cells: key to successful immunotherapy?,Nature Reviews Immunology

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Precursor exhausted T cells: key to successful immunotherapy?
Nature Reviews Immunology ( IF 67.7 ) Pub Date : 2019-10-07 , DOI: 10.1038/s41577-019-0223-7
Axel Kallies ₁ , Dietmar Zehn ₂ , Daniel T Utzschneider ₁

Affiliation

Cytotoxic T cell immunity in response to chronic infections and tumours is maintained by a specialized population of CD8+ T cells that exhibit hallmarks of both exhausted and memory cells and give rise to terminally differentiated exhausted effector cells that contribute to viral or tumour control. Importantly, recent work suggests these cells, which we refer to as 'precursor exhausted' T (TPEX) cells, are responsible for the proliferative burst that generates effector T cells in response to immune checkpoint blockade targeting programmed cell death 1 (PD1), and increased TPEX cell frequencies have recently been linked to increased patient survival. We believe the recent discovery of TPEX cells not only represents a paradigm shift in our understanding of the mechanisms that maintain CD8+ T cell responses in chronic infections and tumours but also opens up unexpected avenues for the development of new and innovative therapeutic approaches. In this Opinion article, we discuss the differentiation and function of TPEX cells and suggest that targeting these cells may be key for successful immunotherapy.

中文翻译：

前体耗尽的T细胞：成功免疫治疗的关键？

专门针对CD8 + T细胞的群体维持了对慢性感染和肿瘤的细胞毒性T细胞免疫力，这些CD8 + T细胞表现出耗尽和记忆细胞的标志，并产生最终分化的耗尽效应细胞，从而有助于控制病毒或肿瘤。重要的是，最近的研究表明，这些细胞（我们称为“前体耗竭” T（TPEX）细胞）是负责响应针对程序性细胞死亡1（PD1）的免疫检查点封锁而产生效应T细胞的增殖爆发的原因，以及TPEX细胞频率增加最近与患者存活率增加有关。我们相信最近发现的TPEX细胞不仅代表了我们对在慢性感染和肿瘤中维持CD8 + T细胞应答的机制的理解发生了范式转变，而且还为开发新的和创新的治疗方法开辟了意想不到的途径。在这篇观点文章中，我们讨论了TPEX细胞的分化和功能，并建议靶向这些细胞可能是成功进行免疫治疗的关键。

更新日期：2019-10-07

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