基于NK细胞的恶性疾病免疫治疗

NK Cell-Based Immunotherapy for Malignant Diseases

摘要: 自然杀伤(NK)细胞是先天性淋巴细胞，具有识别和杀死肿瘤细胞的能力，在抗癌免疫中发挥着重要作用。肿瘤患者的NK细胞具有不同的表型和功能特性，这些特性可能是由肿瘤微环境决定的。控制NK细胞活性的人类白细胞抗原I类特异性抑制性受体的发现，为调节由一系列抑制性受体调节的免疫反应的基本概念铺平了道路，并强调了探索NK细胞在癌症治疗中潜力的重要性。尽管目前正在开发一系列基于NK细胞的方法，但为了提高这些疗法的疗效，仍然需要克服重大挑战。这些包括肿瘤细胞由于表达抑制分子而逃避NK细胞识别、NK细胞的免疫抑制信号、肿瘤的NK细胞浸润减少、免疫抑制微环境和NK细胞在体内的持久性有限。这篇综述将概述NK细胞生物学、NK细胞激活和抑制受体、在实体瘤免疫监视中的作用、导致NK细胞免疫逃逸或免疫监视的肿瘤微环境，以及NK细胞的来源，为以后临床上设计使用NK细胞提供有效策略，提高治疗效果。

Abstract: Natural killer (NK) cells are innate lymphocytes with the ability to recognize and kill tumor cells and play an important role in anti-cancer immunity. NK cells from tumor patients have different phenotypic and functional properties that may be determined by the tumor microenvironment. The discovery of human leukocyte antigen class I-specific inhibitory receptors controlling NK cell activi-ty has paved the way for the fundamental concept of modulating immune responses regulated by a range of inhibitory receptors and underscores the importance of exploring the potential of NK cells in cancer therapy. Although a range of NK cell-based approaches are currently being developed, significant challenges still need to be overcome in order to improve the efficacy of these therapies. These include tumor cells evading NK cell recognition due to the expression of inhibitory molecules, immunosuppressive signaling by NK cells, reduced NK cell infiltration of tumors, an immunosup-pressive microenvironment, and limited persistence of NK cells in vivo. This review will provide an overview of NK cell biology, NK cell cytosolic activation and inhibitory receptors, their role in im-munosurveillance in solid tumors, the tumor microenvironment leading to immune escape or im-munosurveillance of NK cells, and the sources of NK cells, to provide an effective strategy for de-signing the use of NK cells in the future clinic and to improve therapeutic outcomes.