NK Cell Adoptive Immunotherapy of Cancer: Evaluating Recognition Strategies and Overcoming Limitations.
NK Cell Adoptive Immunotherapy of Cancer: Evaluating Recognition Strategies and Overcoming Limitations.
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DOI：
10.1016/j.bbmt.2020.09.030
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发表时间：
2021-01
影响因子：
3.2
通讯作者：
Cruz CRY
中科院分区：
文献类型：
--
作者：
Sanchez CE;Dowlati EP;Geiger AE;Chaudhry K;Tovar MA;Bollard CM;Cruz CRY
自然杀伤（NK）细胞是天然免疫系统的主要效应细胞，通过以下多种策略识别肿瘤细胞：（1）检测激活受体配体的存在，这些配体在癌症中常常上调；（2）靶向主要组织相容性复合体（MHC）缺失的细胞；（3）结合与肿瘤细胞表面肿瘤特异性抗原结合的抗体。所有这些策略都已成功应用于针对癌症的过继性NK细胞免疫疗法中。在这篇综述中，我们回顾了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类似，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以及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从与其他免疫治疗药物的联合疗法中获益。
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.
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