肿瘤免疫微环境中的NK 细胞及免疫治疗

自然杀伤（NK）细胞是一类具有强大抗肿瘤功能的固有淋巴细胞，能够快速识别和杀伤肿瘤细胞，其功能受活化性受 体和抑制性受体的多种信号所调控。但是，肿瘤浸润NK 细胞的杀伤功能由于免疫抑制性肿瘤微环境而失调，甚至会促进肿瘤细胞的免疫逃逸，导致多种免疫疗法临床治疗的效果不佳。肿瘤细胞上调表达抑制性配体、肿瘤微环境中大量抑炎因子及异常的 低氧、低pH 等，都诱导肿瘤浸润NK 细胞杀伤功能受损。近年来，关于肿瘤微环境与肿瘤浸润NK 细胞的研究正处于肿瘤免疫领 域的前沿，已经取得了很多临床研究成果。多项研究表明，肿瘤浸润NK 细胞通常表现为抑制性受体上调、活化性受体下调和代 谢异常等特征，基于此，研究者开发了多种针对性治疗方案，以恢复NK 细胞的杀伤能力。本文在阐述NK 细胞功能活化和抑制 相关机制的基础上，论述了肿瘤浸润NK 细胞的特征及其相应的肿瘤免疫治疗方案。

NK cells within tumor immune microenvironment and immunotherapy

Natural killer (NK) cells, a kind of innate lymphocyte with strong anti-tumor function, can quickly recognize and kill tumor cells. Their function is regulated by a variety of signals of activating and inhibitory receptors. However, the killing function of tumor-infiltrating NK cell is dysregulated due to the immunosuppressive tumor microenvironment, which may even promote the immune escape of tumor cells, resulting in poor clinical therapeutic effects of various immunotherapies. Up-regulated expression of inhibitory ligands on tumor cells, a large number of anti-inflammatory cytokines in the tumor microenvironment, abnormal hypoxia, low pH, and other indicators induced impaired killing function of tumor-infiltrating NK cells. In recent years, the research on tumor microenvironment and tumor infiltrating NK cells is at the forefront of tumor immunity, and many clinical research results have been achieved. Many studies have shown that tumor-infiltrating NK cells are usually characterized by up-regulation of inhibitory receptors, down-regulation of activating receptors, and abnormal metabolism. Based on this, researchers have developed many targeted therapies to restore the killing function of NK cells. In this paper, we summarize the characteristics of tumor-infiltrating NK cells and the related tumor immunotherapies based on the mechanisms of activation and inhibition of NK cell function.