A DNA-based cancer vaccine enhances lymphocyte cross talk by engaging the NKG2D receptor.
A DNA-based cancer vaccine enhances lymphocyte cross talk by engaging the NKG2D receptor.
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DOI：
10.1182/blood-2005-10-4231
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发表时间：
2006-04
期刊：
影响因子：
20.3
通讯作者：
He Zhou;Yunping Luo;C. Kaplan;J. A. Krüger;Sung‐Hyung Lee;R. Xiang;R. Reisfeld
中科院分区：
文献类型：
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作者：
He Zhou;Yunping Luo;C. Kaplan;J. A. Krüger;Sung‐Hyung Lee;R. Xiang;R. Reisfeld
NKG 2D受体是一种在NK细胞和活化的CD 8 T细胞上表达的刺激性受体。我们以前证明，参与NKG 2D受体显着提高了基于生存素的DNA疫苗的疗效。编码NKG 2D配体H60和生存素的组合疫苗激活先天性和适应性抗肿瘤免疫，并导致对不同来源和NKG 2D表达水平的肿瘤的更好保护。在这里，我们证明了增强的疫苗效力部分归因于淋巴细胞之间的串扰增加。在引发期间CD 8 T细胞的消耗降低了疫苗诱导的树突状细胞（DC）活化和NK细胞活性。在引发期间NK细胞的耗尽导致DC活化和CTL活性降低。然而，CD 4 T细胞的耗竭导致DC、NK细胞和CD 8 T细胞的活化并增强NK细胞活性。pH 60/存活素疫苗还增加了DC和NK细胞，但减少了CD 4 T细胞归巢到派尔集合淋巴结，这可能是归巢受体谱变化的结果。因此，通过优先激活和吸引阳性调节剂并减少派尔集合淋巴结中的阴性调节剂，这种双功能DNA疫苗诱导更适合NK细胞激活和T细胞引发的微环境。
The NKG2D receptor is a stimulatory receptor expressed on NK cells and activated CD8 T cells. We previously demonstrated that engaging the NKG2D receptor markedly improved the efficacy of a survivin-based DNA vaccine. The combination vaccine, encoding both the NKG2D ligand H60 and survivin, activates innate and adaptive antitumor immunity and results in better protection against tumors of different origin and NKG2D expression levels. Here we demonstrate that the enhanced vaccine efficacy is in part attributable to increased cross talk between lymphocytes. Depletion of CD8 T cells during priming reduces the vaccine-induced activation of dendritic cells (DCs) and NK cell activity. Depletion of NK cells during priming leads to reduced DC activation and CTL activity. However, depletion of CD4 T cells results in the activation of DCs, NK cells, and CD8 T cells and enhances NK cell activity. The pH60/Survivin vaccine also increases DCs and NK cells but decreases CD4 T cell homing to Peyer patches, presumably as a result of changes in the homing receptor profile. Thus, by preferentially activating and attracting positive regulators and reducing negative regulators in Peyer patches, this dual-function DNA vaccine induces a microenvironment more suitable for NK cell activation and T cell priming.