文章：

自然杀伤细胞在抗肿瘤过继细胞免疫治疗中的作用

Natural killer cells in antitumour adoptive cell immunotherapy

原文发布日期：2022-07-25

DOI: 10.1038/s41568-022-00491-0

类型: Review Article

开放获取: 否

英文摘要：

Natural killer (NK) cells comprise a unique population of innate lymphoid cells endowed with intrinsic abilities to identify and eliminate virally infected cells and tumour cells. Possessing multiple cytotoxicity mechanisms and the ability to modulate the immune response through cytokine production, NK cells play a pivotal role in anticancer immunity. This role was elucidated nearly two decades ago, when NK cells, used as immunotherapeutic agents, showed safety and efficacy in the treatment of patients with advanced-stage leukaemia. In recent years, following the paradigm-shifting successes of chimeric antigen receptor (CAR)-engineered adoptive T cell therapy and the advancement in technologies that can turn cells into powerful antitumour weapons, the interest in NK cells as a candidate for immunotherapy has grown exponentially. Strategies for the development of NK cell-based therapies focus on enhancing NK cell potency and persistence through co-stimulatory signalling, checkpoint inhibition and cytokine armouring, and aim to redirect NK cell specificity to the tumour through expression of CAR or the use of engager molecules. In the clinic, the first generation of NK cell therapies have delivered promising results, showing encouraging efficacy and remarkable safety, thus driving great enthusiasm for continued innovation. In this Review, we describe the various approaches to augment NK cell cytotoxicity and longevity, evaluate challenges and opportunities, and reflect on how lessons learned from the clinic will guide the design of next-generation NK cell products that will address the unique complexities of each cancer.

摘要翻译： 

自然杀伤细胞（NK细胞）构成了一类独特的先天淋巴样细胞群，天生具有识别和清除病毒感染的细胞及肿瘤细胞的能力。NK细胞拥有多种细胞毒性机制，并能通过产生细胞因子来调节免疫反应，在抗癌免疫中发挥着关键作用。这一角色在近二十年前得以阐明，当时NK细胞作为免疫治疗剂，在治疗晚期白血病患者中显示出安全性和有效性。近年来，随着嵌合抗原受体改造的过继性T细胞疗法取得颠覆性成功，以及将细胞转化为强大抗肿瘤武器的技术进步，NK细胞作为免疫治疗候选对象的关注度呈指数级增长。基于NK细胞的治疗策略侧重于通过共刺激信号、检查点抑制和细胞因子装甲来增强NK细胞的效力和持久性，并旨在通过表达CAR或使用衔接分子来重定向NK细胞对肿瘤的特异性。在临床中，第一代NK细胞疗法已取得了令人鼓舞的结果，显示出良好的疗效和显著的安全性，从而推动了持续创新的巨大热情。本综述中，我们阐述了增强NK细胞毒性和寿命的各种方法，评估了挑战与机遇，并思考了从临床实践中获得的经验如何指导下一代NK细胞产品的设计，以应对每种癌症独特的复杂性。

原文链接：

Natural killer cells in antitumour adoptive cell immunotherapy