NK细胞抑制性受体与肿瘤免疫治疗综述

Inhibitory receptors of NK cells and tumor immunotherapy

自然杀伤(natural killer,NK)细胞通过其固有受体识别方式,直接、快速杀伤靶细胞,对抗肿瘤免疫至关重要。NK细胞的激活很大程度上受到了其本身抑制性受体的负性调控,但是在肿瘤微环境下这些抑制性受体通常是发生免疫逃逸的重要途径之一。近年来KIR、NKG2A、TIGIT及CD96免疫检查点抑制剂的临床前和临床试验显示,肿瘤中NK细胞功能衰竭可被逆转,进而增强抗肿瘤免疫。本文对NK细胞抑制性受体与肿瘤免疫逃逸及免疫治疗的进展予以综述。

Natural killer cells(NK cells)can kill target cells directly and rapidly through their intrinsic receptor recognition,serving as important immune cells for anti-tumor therapy.To considerable extent,the activation of NK cells is negatively regulated by inhibitory receptors,but these inhibitory receptors are often utilized to evade immune surveillance in the tumor microenvironment.In recent years,preclinical and clinical trials of blocking antibodies based on KIR,NKG2A,TIGIT and CD96 have shown that NK cell malfunction in tumors can be reversed to enhance anti-tumor immunity.To this end,the functional characteristics of inhibitory receptors found in human NK cells,as well as related tumor immune escape mechanisms and the progress in targeted therapy of cancer immunotherapy are summarized in this article.