Li Yang, Yin Jie, Li Ting, Huang Shan, Yan Han, Leavenworth JianMei, Wang Xi
Department of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Laboratory of Epigenetics in Development and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, 300070, China.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute; Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston, MA, 02115, USA.
Sci China Life Sci. 2015 Dec;58(12):1233-45. doi: 10.1007/s11427-015-4970-9. Epub 2015 Nov 20.
Natural killer (NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex (MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor (CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy.
自然杀伤(NK)细胞能够识别并杀死靶细胞,且不依赖于抗原特异性和主要组织相容性复合体(MHC)匹配,在针对肿瘤的免疫防御中发挥关键作用。然而,肿瘤细胞常常获得逃避NK细胞介导的免疫监视的能力。因此,了解肿瘤环境中NK细胞表型和功能的调控机制,对于设计新方法以改进当前基于细胞的免疫疗法至关重要。在这篇综述中,我们阐述了与NK细胞介导的抗肿瘤活性调控相关的NK细胞的主要生物学特征和分子机制。我们还进一步概述了当前基于NK细胞的癌症治疗的临床方法,包括细胞因子输注、自体或异体NK细胞的过继性转移、表达嵌合抗原受体(CAR)的NK细胞的应用以及记忆样NK细胞的过继性转移。鉴于这些令人鼓舞的临床结果以及对本综述中提出的基本问题的更全面理解,我们预计基于NK细胞的方法在未来癌症免疫治疗中可能具有巨大潜力。