Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
Nat Rev Drug Discov. 2020 Mar;19(3):200-218. doi: 10.1038/s41573-019-0052-1. Epub 2020 Jan 6.
Natural killer (NK) cells can swiftly kill multiple adjacent cells if these show surface markers associated with oncogenic transformation. This property, which is unique among immune cells, and their capacity to enhance antibody and T cell responses support a role for NK cells as anticancer agents. Although tumours may develop several mechanisms to resist attacks from endogenous NK cells, ex vivo activation, expansion and genetic modification of NK cells can greatly increase their antitumour activity and equip them to overcome resistance. Some of these methods have been translated into clinical-grade platforms and support clinical trials of NK cell infusions in patients with haematological malignancies or solid tumours, which have yielded encouraging results so far. The next generation of NK cell products will be engineered to enhance activating signals and proliferation, suppress inhibitory signals and promote their homing to tumours. These modifications promise to significantly increase their clinical activity. Finally, there is emerging evidence of increased NK cell-mediated tumour cell killing in the context of molecularly targeted therapies. These observations, in addition to the capacity of NK cells to magnify immune responses, suggest that NK cells are poised to become key components of multipronged therapeutic strategies for cancer.
自然杀伤 (NK) 细胞如果发现表面标志物与致癌转化相关，就能迅速杀死多个相邻细胞。这种特性在免疫细胞中是独一无二的，它们增强抗体和 T 细胞反应的能力支持 NK 细胞作为抗癌药物的作用。尽管肿瘤可能发展出几种机制来抵抗内源性 NK 细胞的攻击，但 NK 细胞的体外激活、扩增和基因修饰可以大大提高其抗肿瘤活性，并使它们能够克服耐药性。其中一些方法已经转化为临床级别的平台，并支持 NK 细胞输注治疗血液系统恶性肿瘤或实体瘤患者的临床试验，迄今为止取得了令人鼓舞的结果。下一代 NK 细胞产品将经过工程改造以增强激活信号和增殖，抑制抑制信号并促进其向肿瘤归巢。这些修饰有望显著提高它们的临床活性。最后，在分子靶向治疗的背景下，越来越多的证据表明 NK 细胞介导的肿瘤细胞杀伤增加。除了 NK 细胞能够放大免疫反应的能力外，这些观察结果表明 NK 细胞有望成为癌症多管齐下治疗策略的关键组成部分。
