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增强自然杀伤细胞功能以治疗肿瘤和感染的策略。

Strategies to enhance NK cell function for the treatment of tumors and infections.

作者信息

Freund-Brown Jacquelyn, Chirino Leilani, Kambayashi Taku

机构信息

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

出版信息

Crit Rev Immunol. 2018;38(2):105-130. doi: 10.1615/CritRevImmunol.2018025248.

Abstract

Natural killer (NK) cells are innate immune cells equipped with the ability to rapidly kill stressed cells that are neoplastic or virally infected. These cells are especially important in settings where these stressed cells downregulate MHC class I molecules and evade recognition by cytotoxic T cells. However, the activity of NK cells alone is often suboptimal to fully control tumor growth or to clear viral infections. Thus, the enhancement of NK cell function is necessary to fully harness their antitumor or antiviral potential. In this review, we discuss how NK cell function can be augmented by the modulation of signal transduction pathways, by the manipulation of inhibitory/activating receptors on NK cells, and by cytokine-induced activation. We also discuss how some of these strategies are currently impacting NK cells in the treatment of cancer and infections.

摘要

自然杀伤(NK)细胞是先天性免疫细胞,具备快速杀伤发生肿瘤或受到病毒感染的应激细胞的能力。在这些应激细胞下调主要组织相容性复合体(MHC)I类分子并逃避细胞毒性T细胞识别的情况下,这些细胞尤为重要。然而,仅靠NK细胞的活性往往不足以完全控制肿瘤生长或清除病毒感染。因此,增强NK细胞功能对于充分发挥其抗肿瘤或抗病毒潜力是必要的。在这篇综述中,我们讨论了如何通过调节信号转导通路、操纵NK细胞上的抑制性/激活受体以及细胞因子诱导的激活来增强NK细胞功能。我们还讨论了其中一些策略目前在癌症和感染治疗中对NK细胞的影响。

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