Utilizing cytokines to function-enable human NK cells for the immunotherapy of cancer.
Utilizing cytokines to function-enable human NK cells for the immunotherapy of cancer.
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DOI：
10.1155/2014/205796
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发表时间：
2014
期刊：
影响因子：
3.2
通讯作者：
Fehniger TA
中科院分区：
文献类型：
--
作者：
Romee R;Leong JW;Fehniger TA
自然杀伤细胞（NK）是先天淋巴样细胞，在宿主防御病原体和介导抗肿瘤免疫中起重要作用。细胞因子受体转导调节增殖、存活、激活状态和触发效应功能的重要信号。在这里，我们回顾了调节人类NK细胞发育、存活和功能的主要细胞因子的作用，包括IL-2、IL-12、IL-15、IL-18和IL-21，以及它们作为免疫治疗药物在临床中的应用。我们强调NK细胞生物学的最新进展，先天NK细胞记忆的鉴定，并重点关注细胞因子诱导的记忆样NK细胞（CIML），这些细胞是由IL-12、IL-15和IL-18短暂的联合激活引起的。这种激活导致NK细胞在遇到二次刺激时表现出增强的功能，并提供了一种使NK细胞增强对感染和癌症的反应性的新方法。对细胞因子-细胞因子受体信号的细胞和分子方面的理解的提高，导致了对维持和/或激活NK细胞抗肿瘤潜能的细胞因子临床应用的兴趣的复苏。在未来，这些策略将与负调控信号阻断和增强识别相结合，全面增强NK细胞进行免疫治疗。
Natural killer (NK) cells are innate lymphoid cells important for host defense against pathogens and mediate antitumor immunity. Cytokine receptors transduce important signals that regulate proliferation, survival, activation status, and trigger effector functions. Here, we review the roles of major cytokines that regulate human NK cell development, survival, and function, including IL-2, IL-12, IL-15, IL-18, and IL-21, and their translation to the clinic as immunotherapy agents. We highlight a recent development in NK cell biology, the identification of innate NK cell memory, and focus on cytokine-induced memory-like (CIML) NK cells that result from a brief, combined activation with IL-12, IL-15, and IL-18. This activation results in long lived NK cells that exhibit enhanced functionality when they encounter a secondary stimulation and provides a new approach to enable NK cells for enhanced responsiveness to infection and cancer. An improved understanding of the cellular and molecular aspects of cytokine-cytokine receptor signals has led to a resurgence of interest in the clinical use of cytokines that sustain and/or activate NK cell antitumor potential. In the future, such strategies will be combined with negative regulatory signal blockade and enhanced recognition to comprehensively enhance NK cells for immunotherapy.