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Unraveling exhaustion in adaptive and conventional NK cells.
Journal of Leukocyte Biology ( IF 5.5 ) Pub Date : 2020-07-29 , DOI: 10.1002/jlb.4mr0620-091r
Aimee M Merino 1 , Hansol Kim 1 , Jeffrey S Miller 1 , Frank Cichocki 1
Affiliation  

Immune exhaustion in T cells significantly impacts their ability to control malignancies and infections, and its discovery has led to revolutionary therapies for cancer in the form of checkpoint blockade. NK cells, like T cells, are lymphocytes that recognize virally infected and malignantly transformed cells. However, it remains unclear if NK cells are similarly susceptible to exhaustion. In this review, the aims are to summarize what is currently known and to identify key areas of variability that skew the scientific literature on NK cell exhaustion. A lack of consensus on the defining features of NK cell dysfunctional states such as senescence, suppression, and exhaustion has made a comparison between studies difficult. There are also significant differences in the biology of NK cell subsets with long‐lived, adaptive NK cells sharing an epigenetic signature closer to memory CD8+ T cells than to conventional NK cells. Very different checkpoint receptor expression and effector functions have been shown in adaptive versus conventional NK cells chronically exposed to activating signals. Adaptive NK cells develop in individuals with cytomegalovirus (CMV) infection and well over half of the human population worldwide is CMV seropositive by adulthood. Despite this high prevalence, most studies do not account or control for this population. This may contribute to some of the variability reported in the literature on checkpoint receptor expression on NK cells. In this review, the protective role that exhaustion plays in T cells will also be discussed and the evidence for a similar phenomenon in NK cells will be examined.

中文翻译:

揭示适应性和常规 NK 细胞的衰竭。

T 细胞中的免疫衰竭会显着影响它们控制恶性肿瘤和感染的能力,它的发现导致了检查点封锁形式的革命性癌症疗法。NK 细胞与 T 细胞一样,是识别病毒感染和恶性转化细胞的淋巴细胞。然而,尚不清楚 NK 细胞是否同样容易衰竭。在这篇综述中,目的是总结目前已知的情况,并确定导致 NK 细胞耗竭的科学文献出现偏差的关键变异领域。对于 NK 细胞功能失调状态的定义特征(如衰老、抑制和衰竭)缺乏共识,使得研究之间的比较变得困难。NK细胞亚群的生物学也存在显着差异,+  T 细胞优于传统的 NK 细胞。在长期暴露于激活信号的适应性和常规 NK 细胞中,已经显示出非常不同的检查点受体表达和效应器功能。适应性 NK 细胞在患有巨细胞病毒 (CMV) 感染的个体中发育,并且全世界超过一半的人口在成年时为 CMV 血清反应阳性。尽管患病率很高,但大多数研究并未考虑或控制这一人群。这可能导致文献中报道的关于 NK 细胞检查点受体表达的一些变异性。在这篇综述中,还将讨论衰竭在 T 细胞中所起的保护作用,并检查在 NK 细胞中存在类似现象的证据。
更新日期:2020-09-30
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