Regulatory Mechanisms and Reversal of CD8(+)T Cell Exhaustion: A Literature Review.
Regulatory Mechanisms and Reversal of CD8(+)T Cell Exhaustion: A Literature Review.
复制标题
CD8（+）T细胞耗尽的调节机制和逆转：文献综述。
作者：
几十年来，免疫T细胞，特别是由于其强大的抗原导向的细胞毒作用，已经成为免疫系统参与抗癌斗争的中心焦点。人们对利用T细胞进行癌症免疫治疗的兴趣正在迅速增长。最新的临床研究旨在有效地使用免疫检查点抑制剂(ICI)药物治疗癌症患者。然而，T细胞可以建立保护性的抗肿瘤反应，或者相反，T细胞可以引起严重的功能障碍，从而促进大多数慢性感染患者的疾病进展。这种矛盾在很大程度上取决于免疫T细胞与肿瘤微环境周围的其他肿瘤浸润性细胞或炎性细胞因子之间的相互作用。鉴于逆转T细胞耗竭必将成为临床肿瘤免疫治疗的生物标志物，本文就CD8+T细胞耗竭的研究现状及调控机制作一综述。CD8+T细胞耗竭是慢性感染和肿瘤进展过程中T细胞功能障碍的一种状态。疲惫的CD8+T细胞以低效应功能、高抑制受体表达、独特的代谢模式和转录谱改变为特征。近年来，对肿瘤免疫治疗中与T细胞耗竭相关的调节机制的认识和干预的进展引起了该领域的更多关注。因此，我们强调CD8+T细胞耗竭的典型特征和相关机制，特别是其逆转的可能性，这对免疫治疗具有临床意义。
It has been known for decades that immune T cells, especially due to their capacity for powerful antigen-directed cytotoxicity, have become a central focus for engaging the immune system in the fight against cancer. Interest in harnessing T cells for cancer immunotherapy is rapidly growing. The latest clinical research aims to effectively use immune checkpoint inhibitor (ICI) drugs to treat cancer patients. However, T cells can either establish a protective antitumor response, or, in contrast, induce severe dysfunction that promotes disease progression in the majority of chronic infection patients. The contradiction depends, to a large degree, on the interaction between immune T cells and other tumor infiltrating cells or inflammatory cytokines around the tumor microenvironment. This review aims to summarize the current knowledge and regulatory mechanisms of CD8+T cell exhaustion, since reversing T cell exhaustion will definitely become a biomarker of clinical tumor immunotherapy. CD8+T cell exhaustion is a state of T cell dysfunction during chronic infection and tumor progression. Exhausted CD8+T cells are characterized by low effector function, high expression of inhibitory receptors, unique metabolic patterns, and altered transcriptional profiles. Recently, advances in understanding and interfering with the regulatory mechanisms associated with T cell exhaustion in tumor immunotherapy have brought greater attention to the field. Therefore, we emphasize the typical features and related mechanisms of CD8+T cell exhaustion and particularly the potential for its reversal, which has clinical implications for immunotherapy.
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影响因子：
30.5
作者：
Boi, Shannon K.;Lan, Xin;Youngblood, Ben
通讯作者：
Youngblood, Ben
影响因子：
10.1
作者：
Deng, Jie;Li, Jiannan;Mabaera, Rodwell
通讯作者：
Mabaera, Rodwell
影响因子：
64.8
作者：
Day, Cheryl L.;Kaufmann, Daniel E.;Walker, Bruce D.
通讯作者：
Walker, Bruce D.
DOI：
10.1073/pnas.0801497105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Blackburn, Shawn D.;Shin, Haina;Wherry, E. John
通讯作者：
Wherry, E. John
DOI：
10.4049/jimmunol.1002042
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Banerjee A;Gordon SM;Intlekofer AM;Paley MA;Mooney EC;Lindsten T;Wherry EJ;Reiner SL
通讯作者：
Reiner SL