NK-cell activation by LIGHT triggers tumor-specific CD8+ T-cell immunity to reject established tumors
NK-cell activation by LIGHT triggers tumor-specific CD8+ T-cell immunity to reject established tumors
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DOI：
10.1182/blood-2005-08-3485
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发表时间：
2006-02-15
期刊：
影响因子：
20.3
通讯作者：
Fu, YX
中科院分区：
文献类型：
--
作者：
Fan, ZS;Yu, P;Fu, YX
自然杀伤(NK)细胞通常被认为是杀死病毒感染和转化细胞的先天效应细胞。目前尚不清楚NK细胞如何激发获得性免疫来根除肿瘤。我们现在证明，肿瘤坏死因子超家族成员LIGH，被称为TNFSF14和T细胞共刺激分子，是激活NK细胞的关键配体。疱疹病毒进入介体(Hvem)在NK细胞上表达，其与LIGH的结合介导NK细胞的活化。粗鲁的举止。NK和CD8(+)细胞对肿瘤的排斥都是必要的，但不是充分的，因为缺乏这两种细胞的小鼠都无法排斥肿瘤。有趣的是，激活的NK细胞不会直接杀死肿瘤，但可以通过依赖干扰素的方式促进肿瘤特异性CD8(+)T细胞的启动。相反，肿瘤进展过程中NK细胞或干扰素-γ的缺失破坏了CD8(+)细胞介导的肿瘤排斥反应，这表明肿瘤是NK和CD8(+)细胞之间相互干扰的重要部位。此外，缺乏IFNG的NK细胞不能有效地激活CD8(+)T细胞，提示干扰素-γ在NK介导的细胞毒性T淋巴细胞(CTL)激活中起重要作用。我们的发现确立了LIGH在NK激活/扩张中的直接作用，以及激活的NK细胞在启动CD8(+)T细胞和打破肿瘤部位T细胞耐受性方面的关键辅助作用。
Natural killer (NK) cells are generally reported as innate effector cells for killing virally infected and transformed cells. It is unclear how NK cells evoke adaptive immunity to eradicate tumors. We now demonstrate that the TNF superfamily member, LIGHT, known as TNFSF14 and a T-cell costimulatory molecule, is a critical ligand for the activation of NK cells. Herpesvirus entry mediator (HVEM) is expressed on NK cells, and its engagement with LIGHT mediates NK-cell activation. dent manner. Both NK and CD8(+) cells are essential but not sufficient for the rejection of tumors because mice lacking either population fail to reject the tumor. Interestingly, activated NK cells do not kill tumors directly but can facilitate the priming of tumor-specific CD8(+) T cells in an IFN-gamma-dependent manner. Conversely, intratumor depletion of either NK cells or IFN-gamma during tumor progression disrupts CD8(+) cell-mediated tumor rejection, suggesting that the tumor is the essential site for the crosstalk between NK and CD8(+) cells. Furthermore, IFNG-deficient NK cells fail to effectively activate CD8(+) T cells, suggesting IFN-gamma plays an important role in NK-mediated activation of cytotoxic T lymphocytes (CTLs). Our findings establish a direct role for LIGHT in NK activation/expansion and a critical helper role of activated NK cells in priming CD8(+) T cells and breaking T-cell tolerance at the tumor site.