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调节 NK 细胞代谢用于癌症免疫治疗。

Modulating NK cell metabolism for cancer immunotherapy.

机构信息

Biocruces Bizkaia Health Research Institute, Immunopathology Group, Barakaldo, Spain.

Biocruces Bizkaia Health Research Institute, Immunopathology Group, Barakaldo, Spain.

出版信息

Semin Hematol. 2020 Oct;57(4):213-224. doi: 10.1053/j.seminhematol.2020.10.003. Epub 2020 Oct 26.

Abstract

Natural killer (NK) cells are lymphocytes with potent antitumor functions and, therefore, multiple NK cell-based cancer immunotherapies have been developed and are currently being tested. However, there is a necessity to find new means to improve these therapies, and immunometabolism represents an attractive target. NK cell effector functions are intricately linked to their metabolism, and modulating the latter could be the key to release their full potential. In this review, we have summarized how NK cell metabolism is regulated during some processes, such as maturation, viral infection, and cytokine stimulation. Additionally, we provide an overview of how NK cell metabolism is affected by current therapeutic approaches aimed to promote NK cell expansion and/or to increase their effector functions. We have also recapitulated several strategies that could help alleviating the metabolic impairment that characterizes tumor-infiltrating NK cells, and thus increase or restore their effector functions. Furthermore, we have reviewed several therapeutic approaches targeting cancer metabolism that could synergize with NK cell-based cancer immunotherapies, and thus enhance their efficacy.

摘要

自然杀伤 (NK) 细胞是具有强大抗肿瘤功能的淋巴细胞,因此已经开发出多种基于 NK 细胞的癌症免疫疗法,目前正在进行测试。然而,有必要寻找新的方法来改进这些疗法,而免疫代谢是一个有吸引力的靶点。NK 细胞的效应功能与其代谢密切相关,调节后者可能是释放其全部潜力的关键。在这篇综述中,我们总结了 NK 细胞代谢在成熟、病毒感染和细胞因子刺激等过程中是如何被调节的。此外,我们还概述了当前旨在促进 NK 细胞扩增和/或增强其效应功能的治疗方法如何影响 NK 细胞代谢。我们还总结了几种策略,可以帮助减轻浸润肿瘤的 NK 细胞的代谢损伤,从而增加或恢复其效应功能。此外,我们还回顾了几种针对癌症代谢的治疗方法,这些方法可以与基于 NK 细胞的癌症免疫疗法协同作用,从而提高其疗效。

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