NK细胞耗竭与卡控点免疫治疗

天然杀伤细胞(NK细胞)作为宿主免疫的第一道防线,通过直接抗肿瘤或辅助T细胞等方式,在抗肿瘤免疫应答过程中发挥重要作用。然而NK细胞在肿瘤微环境中往往处于功能低下的免疫耗竭状态,伴随着异常表达的细胞表面受体谱系,限制着NK细胞效应功能的发挥。NK细胞的卡控点免疫治疗作为肿瘤治疗的崭新思路,主要通过阻断NK细胞表面抑制性受体,解除NK细胞在肿瘤局部接收到的抑制性信号,逆转NK细胞的肿瘤免疫耗竭状态,从而触发抗肿瘤效应。随着研究的深入,我们将进一步揭示NK细胞特定卡控点分子的作用机理、适应证及生物标志物,从而充分发挥NK细胞卡控点免疫治疗的潜力。

NK cell exhaustion and NK-based checkpoint blockade immunotherapy

As the first line of defense of the host immune system,natural killer cells play important roles in anti-tumor immunity,either by direct anti-tumor effects,or by assisting T cell immune responses.However,NK cells are usually functionally exhausted in tumor microenvironment,accompanied with dysregulated expression of an array of surface receptors,restricting the effector potentials of NK cells.NK-based checkpoint immunotherapy aims to trigger anti-tumor efficacy by blocking NK cell surface inhibitory receptors,unleashing NK cells from inhibitory signals of the tumor microenvironment,and reversing NK cell exhaustion,representing a novel strategy in cancer therapy.With more in-depth research to reveal the mechanisms of action,indications,and biomarkers for specific NK cell checkpoint molecules,we shall fully exploit the potentials of NK-based checkpoint blockade immunotherapy.