文章：

癌症-自然杀伤细胞免疫周期

The cancer–natural killer cell immunity cycle

原文发布日期：2020-06-24

DOI: 10.1038/s41568-020-0272-z

类型: Review Article

开放获取: 否

英文摘要：

Immunotherapy with checkpoint blockade induces rapid and durable immune control of cancer in some patients and has driven a monumental shift in cancer treatment. Neoantigen-specific CD8+ T cells are at the forefront of current immunotherapy strategies, and the majority of drug discovery and clinical trials revolve around further harnessing these immune effectors. Yet the immune system contains a diverse range of antitumour effector cells, and these must function in a coordinated and synergistic manner to overcome the immune-evasion mechanisms used by tumours and achieve complete control with tumour eradication. A key antitumour effector is the natural killer (NK) cells, cytotoxic innate lymphocytes present at high frequency in the circulatory system and identified by their exquisite ability to spontaneously detect and lyse transformed or stressed cells. Emerging data show a role for intratumoural NK cells in driving immunotherapy response and, accordingly, there have been renewed efforts to further elucidate and target the pathways controlling NK cell antitumour function. In this Review, we discuss recent clinical evidence that NK cells are a key immune constituent in the protective antitumour immune response and highlight the major stages of the cancer–NK cell immunity cycle. We also perform a new analysis of publicly available transcriptomic data to provide an overview of the prognostic value of NK cell gene expression in 25 tumour types. Furthermore, we discuss how the role of NK cells evolves with tumour progression, presenting new opportunities to target NK cell function to enhance cancer immunotherapy response rates across a more diverse range of cancers.

摘要翻译： 

采用检查点阻断的免疫疗法可在部分患者中诱导快速且持久的癌症免疫控制，推动了癌症治疗的重大变革。新抗原特异性CD8+T细胞是当前免疫治疗策略的核心，大多数药物研发和临床试验都围绕进一步利用这些免疫效应器展开。然而免疫系统包含多样化的抗肿瘤效应细胞，这些细胞必须以协同方式发挥作用，才能克服肿瘤采用的免疫逃逸机制，实现肿瘤根除的完全控制。自然杀伤（NK）细胞作为关键抗肿瘤效应器，是循环系统中高频率存在的细胞毒性先天淋巴细胞，以其自发识别并裂解转化或应激细胞的卓越能力而著称。新兴数据显示肿瘤内NK细胞在驱动免疫治疗应答中发挥作用，因此学界重新致力于进一步阐明并靶向调控NK细胞抗肿瘤功能的通路。本综述将讨论NK细胞在保护性抗肿瘤免疫应答中作为关键免疫成分的最新临床证据，重点阐述癌症-NK细胞免疫周期的主要阶段。我们还对公开转录组数据进行了新颖分析，系统评估NK细胞基因表达在25种肿瘤类型中的预后价值。此外，我们探讨了NK细胞作用如何随肿瘤进展演变，为靶向NK细胞功能、提高更多种类癌症的免疫治疗应答率提供了新机遇。

原文链接：

The cancer–natural killer cell immunity cycle