Program for Cell Enhancement and Technologies for Immunotherapy and Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC.
Department of Neurosurgery, Georgetown University Hospital, Washington, DC.
Transplant Cell Ther. 2021 Jan;27(1):21-35. doi: 10.1016/j.bbmt.2020.09.030. Epub 2020 Sep 29.
Natural killer (NK) cells, the primary effector cells of the innate immune system, utilize multiple strategies to recognize tumor cells by (1) detecting the presence of activating receptor ligands, which are often upregulated in cancer; (2) targeting cells that have a loss of major histocompatibility complex (MHC); and (3) binding to antibodies that bind to tumor-specific antigens on the tumor cell surface. All these strategies have been successfully harnessed in adoptive NK cell immunotherapies targeting cancer. In this review, we review the applications of NK cell therapies across different tumor types. Similar to other forms of immunotherapy, tumor-induced immune escape and immune suppression can limit NK cell therapies' efficacy. Therefore, we also discuss how these limitations can be overcome by conferring NK cells with the ability to redirect their tumor-targeting capabilities and survive the immune-suppressive tumor microenvironment. Finally, we also discuss how future iterations can benefit from combination therapies with other immunotherapeutic agents.
自然杀伤 (NK) 细胞是先天免疫系统的主要效应细胞，通过以下几种策略来识别肿瘤细胞：(1) 检测激活受体配体的存在，这些配体在癌症中常被上调；(2) 靶向 MHC 缺失的细胞；(3) 与结合在肿瘤细胞表面的肿瘤特异性抗原的抗体结合。所有这些策略都已成功应用于针对癌症的过继性 NK 细胞免疫疗法。在这篇综述中，我们将综述 NK 细胞疗法在不同肿瘤类型中的应用。与其他形式的免疫疗法一样，肿瘤诱导的免疫逃逸和免疫抑制会限制 NK 细胞疗法的疗效。因此，我们还讨论了如何通过赋予 NK 细胞重新定向其肿瘤靶向能力和在免疫抑制性肿瘤微环境中存活的能力来克服这些限制。最后，我们还讨论了未来的迭代如何受益于与其他免疫治疗药物的联合治疗。
