Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA, USA.
Nat Rev Drug Discov. 2022 Aug;21(8):559-577. doi: 10.1038/s41573-022-00413-7. Epub 2022 Mar 21.
Natural killer (NK) cells have crucial roles in the innate immunosurveillance of cancer and viral infections. They are 'first responders' that can spontaneously recognize abnormal cells in the body, rapidly eliminate them through focused cytotoxicity mechanisms and potently produce pro-inflammatory cytokines and chemokines that recruit and activate other immune cells to initiate an adaptive response. From the initial discovery of the diverse cell surface receptors on NK cells to the characterization of regulatory events that control their function, our understanding of the basic biology of NK cells has improved dramatically in the past three decades. This advanced knowledge has revealed increased mechanistic complexity, which has opened the doors to the development of a plethora of exciting new therapeutics that can effectively manipulate and target NK cell functional responses, particularly in cancer patients. Here, we summarize the basic mechanisms that regulate NK cell biology, review a wide variety of drugs, cytokines and antibodies currently being developed and used to stimulate NK cell responses, and outline evolving NK cell adoptive transfer approaches to treat cancer.
自然杀伤 (NK) 细胞在癌症和病毒感染的先天免疫监测中起着至关重要的作用。它们是“急救员”，可以自发识别体内的异常细胞，通过集中的细胞毒性机制迅速消除它们，并有效地产生促炎细胞因子和趋化因子，招募和激活其他免疫细胞以启动适应性反应。从最初发现 NK 细胞表面的多种受体，到描述控制其功能的调节事件，我们对 NK 细胞基础生物学的理解在过去三十年中得到了显著提高。这一先进的知识揭示了更复杂的机制，为开发大量令人兴奋的新疗法打开了大门，这些疗法可以有效地操纵和靶向 NK 细胞的功能反应，特别是在癌症患者中。在这里，我们总结了调节 NK 细胞生物学的基本机制，回顾了目前正在开发和使用的各种药物、细胞因子和抗体，以刺激 NK 细胞的反应，并概述了不断发展的 NK 细胞过继转移方法来治疗癌症。
