J Clin Invest. 2019 Apr 15;129(5):1839-1841. doi: 10.1172/JCI128480.
The equilibrium of signaling through activating and inhibitory receptors dictates whether a given NK cell will execute cellular cytotoxicity. In this issue of the JCI, Kamiya et al. describe a novel approach to efficiently inhibiting surface expression of the inhibitory receptor CD94/NK group 2 member A (NKG2A) through retention of the protein in the endoplasmic reticulum. In adoptive transfer experiments into tumor-bearing immunodeficient mice, NKG2Anull NK cells were significantly more effective at eliminating HLA-E-expressing tumor cells than NKG2A+ NK cells. This study provides proof of concept for a new immunotherapeutic approach using NKG2Anull NK cells.
激活和抑制性受体的信号平衡决定了给定的 NK 细胞是否会执行细胞毒性。在本期 JCI 中，Kamiya 等人描述了一种通过将蛋白质保留在内质网中从而有效抑制抑制性受体 CD94/NK 组 2 成员 A（NKG2A）表面表达的新方法。在过继转移实验中，将 NKG2A 缺失的 NK 细胞输入到荷瘤免疫缺陷小鼠中，与 NKG2A+ NK 细胞相比，它们更有效地消除 HLA-E 表达的肿瘤细胞。这项研究为使用 NKG2A 缺失的 NK 细胞的新免疫治疗方法提供了概念验证。
