Precursor exhausted T cells: key to successful immunotherapy?
Precursor exhausted T cells: key to successful immunotherapy?
复制标题
DOI：
10.1038/s41577-019-0223-7
复制
发表时间：
2020-02-01
影响因子：
100.3
通讯作者：
Utzschneider, Daniel T.
中科院分区：
文献类型：
--
作者：
Kallies, Axel;Zehn, Dietmar;Utzschneider, Daniel T.
最近的研究揭示了一个专门的“耗尽”的CD 8（+）T细胞群体，它扩展了癌症的免疫检查点阻断疗法，并可能解释T细胞反应如何在慢性疾病中维持。在这里，作者描述了它们的表型，发育和功能特征，以及为什么它们应该被用于成功的免疫治疗。细胞毒性T细胞免疫应答慢性感染和肿瘤是由一个专门的CD 8（+）T细胞群体，表现出耗尽和记忆细胞的标志，并产生终末分化的耗尽效应细胞，有助于病毒或肿瘤控制。重要的是，最近的工作表明，这些细胞，我们称之为“前体耗尽”的T（T-PEX）细胞，负责增殖爆发，产生效应T细胞，以响应免疫检查点阻断靶向程序性细胞死亡1（PD 1），增加T-PEX细胞频率最近与增加患者生存率有关。我们认为，最近发现的T-PEX细胞不仅代表了我们对慢性感染和肿瘤中维持CD 8（+）T细胞反应机制的理解的范式转变，而且还为开发新的创新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T-PEX细胞的分化和功能，并建议靶向这些细胞可能是成功免疫治疗的关键。
Recent studies have revealed a specialized population of 'exhausted' CD8(+) T cells that expands on immune checkpoint blockade therapy for cancer and may explain how T cell responses are maintained in chronic conditions. Here, the authors describe their phenotypic, developmental and functional characteristics and why they should be harnessed for successful immunotherapy.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 (T-PEX) 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 T-PEX cell frequencies have recently been linked to increased patient survival. We believe the recent discovery of T-PEX 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 T-PEX cells and suggest that targeting these cells may be key for successful immunotherapy.