Hallett William H D, Murphy William J
Department of Microbiology and Immunology, MS 199, University of Nevada School of Medicine, University of Nevada Reno, Reno, NV 89557, USA.
Semin Cancer Biol. 2006 Oct;16(5):367-82. doi: 10.1016/j.semcancer.2006.07.003. Epub 2006 Jul 7.
Natural Killer (NK) cells can mediate numerous anti-tumor and anti-viral effector functions as well as play important immunoregulatory roles in various disease states. Promoting the ability of NK cells to respond in an immunotherapeutic setting has often been sought by the addition of NK cell-stimulating factors. However, such therapies are often found to be insufficient, which may in part be due to the presence of inhibitory influences on the NK cell. NK cells can respond to a plethora of cytokines which are generated by numerous cell types and these interactions can markedly affect NK cell survival and activity. NK cells also possess multiple activating and inhibiting receptors which can alter their function. Whether the NK cell will become activated or not can depend on a complex balance of activating and inhibitory signals received by the cell and modulation of these signals may shift the balance on NK activation. This review discusses the various activating and inhibitory stimuli which can act on NK cells, and suggests that future NK cell-based therapies consider not only activating stimuli but also removal of possible inhibitory elements which could prevent optimal NK cell function and/or survival.
自然杀伤（NK）细胞可以介导多种抗肿瘤和抗病毒效应功能，并在各种疾病状态中发挥重要的免疫调节作用。在免疫治疗环境中，人们常常通过添加NK细胞刺激因子来提高NK细胞的反应能力。然而，这类疗法往往被发现并不充分，这可能部分归因于对NK细胞存在抑制性影响。NK细胞能够对多种细胞类型产生的大量细胞因子做出反应，这些相互作用会显著影响NK细胞的存活和活性。NK细胞还拥有多种激活和抑制受体，它们可以改变NK细胞的功能。NK细胞是否会被激活取决于细胞接收到的激活和抑制信号的复杂平衡，而这些信号的调节可能会改变NK细胞激活的平衡。本综述讨论了可作用于NK细胞的各种激活和抑制刺激，并建议未来基于NK细胞的疗法不仅要考虑激活刺激，还要消除可能阻碍NK细胞最佳功能和/或存活的抑制因素。
