Cancer Immunotherapies Laboratory, Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
Adv Exp Med Biol. 2020;1273:69-90. doi: 10.1007/978-3-030-49270-0_4.
Natural killer cells are powerful effectors of innate immunity that constitute a first line of defense against cancer. NK cells express an array of germline-encoded receptors which allow them to eliminate transformed cells and spare normal, healthy cells. Owing to their ability to kill circulating tumor cells, NK cells play a major role in the protection against cancer metastases. There is also convincing evidence that NK cells protect against some hematological cancers such as acute myeloid leukemia. However, the importance of NK cells for the control of established solid tumors is rather uncertain. Several mechanisms impede NK cell-mediated elimination of solid tumors, starting with the incapacity of NK cells to infiltrate the core of the tumor. In addition, immune escape mechanisms are at play in both solid and hematological cancers. These include the immunoediting of tumor cells and aberrant chronic inflammation that renders NK cells ineffective. In this chapter, I review the phenotypic characteristics of NK cells within the tumor microenvironment. Furthermore, I describe the mechanisms by which NK cells contribute to antitumor immunity. Finally, I review the different immune-evasion factors that impair NK cell activity against cancer.
自然杀伤细胞是先天免疫的强大效应因子，构成了抵抗癌症的第一道防线。NK 细胞表达一系列胚系编码的受体，使它们能够消除转化细胞，而保留正常、健康的细胞。由于其能够杀死循环肿瘤细胞，NK 细胞在防止癌症转移方面发挥着重要作用。也有令人信服的证据表明 NK 细胞可以预防某些血液系统癌症，如急性髓系白血病。然而，NK 细胞对已建立的实体瘤的控制作用还相当不确定。有几种机制会阻碍 NK 细胞介导的实体瘤消除，首先是 NK 细胞无法浸润肿瘤核心。此外，在实体瘤和血液系统肿瘤中都存在免疫逃逸机制。这些机制包括肿瘤细胞的免疫编辑和导致 NK 细胞失效的异常慢性炎症。在这一章中，我将回顾 NK 细胞在肿瘤微环境中的表型特征。此外，我还描述了 NK 细胞促进抗肿瘤免疫的机制。最后，我回顾了不同的免疫逃逸因素，这些因素会削弱 NK 细胞对癌症的活性。
