Department of General Surgery, Shengjing Hospital of China Medical University, 110004, Shenyang, China.
College of Life and Health Science, Northeastern University, 110819, Shenyang, China.
Signal Transduct Target Ther. 2020 Oct 29;5(1):250. doi: 10.1038/s41392-020-00348-8.
Recent studies have demonstrated the potential of natural killer (NK) cells in immunotherapy to treat multiple types of cancer. NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex. The discovery of the NK's potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers. NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy. The effector role of these cells is reliant on the balance of inhibitory and activating signals. Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation. Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment; this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers. Accordingly, this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function, as well as their potential application in tumor immunotherapy.
最近的研究表明，自然杀伤 (NK) 细胞在免疫疗法中具有治疗多种癌症的潜力。NK 细胞是先天淋巴细胞，在肿瘤监测和控制中发挥着重要作用，能够有效杀死肿瘤，而不需要主要组织相容性复合体。NK 细胞作为癌症治疗的有前途的靶点的发现，让肿瘤学家感到欣慰，因为他们面临着化疗耐药性癌症增加的挑战。NK 细胞对实体瘤和血液系统肿瘤具有很大的潜力，并已逐渐显示出作为癌症免疫治疗的治疗靶点的潜力。这些细胞的效应功能依赖于抑制性和激活性信号的平衡。了解各种免疫检查点分子在 NK 细胞抑制性受体过度表达时对 NK 细胞耗竭和损伤的作用，在癌症免疫治疗研究和临床实施中尤为重要。已经发现，新兴的免疫检查点受体和分子介导了肿瘤微环境中 NK 细胞功能障碍；这就需要进一步探索可能被利用来增强对难治性癌症的免疫反应的其他 NK 细胞相关免疫检查点。因此，本综述将重点介绍关于免疫检查点分子和受体在调节 NK 细胞功能中的作用的最新发现，以及它们在肿瘤免疫治疗中的潜在应用。
