Overcoming T cell exhaustion in infection and cancer.

Overcoming T cell exhaustion in infection and cancer.
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克服感染和癌症中的T细胞耗尽。

DOI:
10.1016/j.it.2015.02.008
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发表时间:
2015-04
影响因子:
16.8
通讯作者:
Wherry EJ
Wherry EJ
中科院分区:
医学1区
文献类型:
--
作者:
Pauken KE;Wherry EJ

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PD - 1:PD - L1通路是T细胞耗竭的核心调节因子,其抑制剂最近已被证明对不同癌症的治疗有效。然而,临床反应不一,这突出表明需要更好地理解PD - 1:PD - L1的作用机制、该通路在对不同肿瘤的免疫中的作用以及PD - 1阻断的分子和细胞效应。在此,我们回顾了T细胞耗竭的分子调控,将近期关于癌症中PD - 1阻断疗法的研究结果置于对慢性感染期间PD - 1:PD - L1通路在T细胞耗竭中作用的更广泛理解的背景下。我们讨论了目前对逆转T细胞耗竭所涉及机制的理解,并概述了未来基础和临床研究的关键重点领域。
Inhibitors of the PD-1:PD-L1 pathway, a central regulator of T cell exhaustion, have been recently shown to be effective for treatment of different cancers. However, clinical responses are mixed, highlighting the need to better understand the mechanisms of action of PD-1:PD-L1, the role of this pathway in immunity to different tumors, and the molecular and cellular effects of PD-1 blockade. Here we review the molecular regulation of T cell exhaustion, placing recent findings on PD-1 blockade therapies in cancer in the context of the broader understanding of the roles of the PD-1:PD-L1 pathway in T cell exhaustion during chronic infection. We discuss the current understanding of the mechanisms involved in reversal T cell exhaustion, and outline critical areas of focus for future research, both basic and clinical.
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发表时间: 2011-05-09
期刊: The Journal of experimental medicine
影响因子: --
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