Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO.
Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO.
Semin Hematol. 2020 Oct;57(4):185-193. doi: 10.1053/j.seminhematol.2020.11.003. Epub 2020 Nov 17.
Natural killer (NK) cells are cytotoxic innate lymphoid cells that protect the host from infection and mediate anti-tumor responses. Classically considered part of the innate immune system, NK cells were previously thought to not possess the specificity or enhanced recall responses associated with adaptive T and B lymphocytes. However, a large body of work has transformed these long-held divisions between innate and adaptive immunity; NK cell memory and memory-like responses are clearly established after hapten exposure, viral infection, and combined cytokine activation. These advances come with opportunities to translate innate NK cell recall responses into the clinic as cancer immunotherapy. Here, we review our current understanding of the heterogeneity of memory and memory-like NK cell responses, with distinct formation, molecular biology, and memory type functions. We elaborate on cytokine-induced memory-like NK cells and highlight their application as adoptive immunotherapy for cancer, and as a platform for engineering optimal NK cell anti-tumor responses.
自然杀伤 (NK) 细胞是细胞毒性固有淋巴细胞,可保护宿主免受感染并介导抗肿瘤反应。NK 细胞传统上被认为是固有免疫系统的一部分,以前被认为不具有与适应性 T 和 B 淋巴细胞相关的特异性或增强的记忆反应。然而,大量的工作改变了固有免疫和适应性免疫之间的这种长期划分;在半抗原暴露、病毒感染和联合细胞因子激活后,NK 细胞记忆和类记忆反应显然已经建立。这些进展为将先天 NK 细胞的回忆反应转化为癌症免疫疗法提供了机会。在这里,我们回顾了我们目前对记忆和类记忆 NK 细胞反应异质性的理解,包括不同的形成、分子生物学和记忆类型功能。我们详细介绍了细胞因子诱导的类记忆 NK 细胞,并强调了它们作为癌症过继免疫疗法的应用,以及作为工程优化 NK 细胞抗肿瘤反应的平台。
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