Department of Genetics, Molecular Cell Biology Laboratory, The Smurfit Institute, Trinity College, Dublin D2, Ireland.
Cell Death Differ. 2010 Apr;17(4):616-23. doi: 10.1038/cdd.2009.206. Epub 2010 Jan 15.
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are indispensable factors in the body's ongoing defence against viral infection and tumor development. CTL/NK cells recognize and kill infected or aberrant target cells by two major pathways: either through introduction of a battery of proteases - called granzymes - to the target cell cytosol, or through TNF superfamily-dependent killing. During granzyme-dependent killing, target cell death is quick and efficient and is mediated by multiple granzymes, acting via redundant cell death pathways. Although granzyme-mediated cell death has been intensively studied, recent work has also hinted at an alternative, proinflammatory role for these enzymes. Thus, in addition to their well-established role as intracellular effectors of target cell death, recent data suggest that granzymes may have an extracellular role in the propagation of immune signals. In this study, we discuss the role of granzymes as central factors in antitumor immunity, as well possible roles for these proteases as instigators of inflammation.
细胞毒性 T 淋巴细胞 (CTL) 和自然杀伤 (NK) 细胞是人体对抗病毒感染和肿瘤发展的持续防御中不可或缺的因素。CTL/NK 细胞通过两种主要途径识别和杀死受感染或异常的靶细胞：一种是将一系列称为颗粒酶的蛋白酶导入靶细胞胞质溶胶，另一种是通过 TNF 超家族依赖性杀伤。在颗粒酶依赖性杀伤中，靶细胞死亡迅速而高效，并由多种颗粒酶介导，通过冗余的细胞死亡途径发挥作用。尽管颗粒酶介导的细胞死亡已被深入研究，但最近的研究也暗示这些酶可能具有另一种促炎作用。因此，除了作为靶细胞死亡的细胞内效应物的既定作用外，最近的数据还表明，颗粒酶可能在外周免疫信号的传播中发挥作用。在本研究中，我们讨论了颗粒酶作为抗肿瘤免疫的核心因素的作用，以及这些蛋白酶作为炎症引发者的可能作用。
