NK细胞受体群谱偏移与肿瘤免疫逃逸及逆转  

Imbalance of NK cell receptors and tumor immune escape as well as reversal strategies

作　　者：张彩[1] 田志刚[2] 

机构地区：[1]山东大学药学院免疫药物学研究所,济南250012 [2]中国科学技术大学免疫学研究所,合肥230026

出　　处：《中国免疫学杂志》2016年第5期609-614,共6页Chinese Journal of Immunology

基　　金：国家重点基础研究发展计划(973)项目(2013CB944901);国家自然科学基金项目(81273220;81472646;91442114)资助

摘　　要：NK细胞功能的发挥取决于其表面活化受体和抑制性受体识别靶细胞表面相应配体后所传递信号的平衡状态。肿瘤在发生发展的过程中进化出许多机制,调控NK细胞活化受体和抑制性受体的表达及肿瘤细胞NK细胞识别的配体表达的平衡状态,通常表现为活化受体/配体表达受到抑制而抑制性受体/配体表达增强的群谱偏移现象,成为肿瘤细胞削弱肿瘤微环境中NK细胞功能、诱导NK细胞免疫耐受甚至功能耗竭,最终导致肿瘤免疫逃逸的重要机制。本文就肿瘤发生发展过程中NK细胞受体/配体表达的失衡与肿瘤免疫逃逸的关系及基于逆转NK受体及其配体失衡的免疫治疗策略(尤其是抑制性受体的Checkpoint阻断疗法和CAR修饰的NK细胞治疗)等方面的研究进展做一综述。The effector functions of NK cells are regulated by integrated signals across the array of stimulatory and inhibitory receptors engaged upon interaction with target cell surface ligands. Tumor cells and tumor microenvironment have evolved several mechanisms to regulate the expression of activating / inhibitory receptors on NK cells or ligands for NK cell receptors on tumor cells,leading to imbalance of NK cell receptors or ligands and negatively influence the activity and function of NK cells,thus finally leading to NK cell tolerance or exhaustion as well as tumor escape. In this review,we focus on the association of imbalance expression of NK cell receptors or ligands and tumor immune escape. We discuss specifically on the development of novel mono- and combinatorial strategies（ particularly the inhibitory receptor checkpoint blockade and CAR-NK therapy） to rescue the imbalance of NK cell receptors and dysfunction of NK cells for successful and effective tumor therapy.

关 键 词：NK细胞 NK细胞受体 肿瘤免疫逃逸 免疫治疗 Checkpoint阻断疗法 CAR-NK 

分 类 号：R392.12[医药卫生—免疫学]