Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation
Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation
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DOI：
10.1182/blood-2008-05-155697
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发表时间：
2009-02-12
期刊：
影响因子：
20.3
通讯作者：
van den Brink, Marcel R. M.
中科院分区：
文献类型：
--
作者：
Jenq, Robert R.;King, Christopher G.;van den Brink, Marcel R. M.
异基因骨髓移植(allo-BMT)受者外源性给予角质形成细胞生长因子(KGF)，支持胸腺上皮细胞，增加胸腺原始T细胞的输出。在这里，我们证明了这种改进的T细胞重建导致了对DNA质粒瘤疫苗的增强反应。荷瘤小鼠在异基因骨髓移植后，经KGF和DNA疫苗治疗后，可提高长期存活率并减轻肿瘤负担。在疫苗接种前进行检测时，接受KGF治疗的allo-BMT受者的外周T细胞数量增加，包括具有疫苗识别潜力的CD8(+)T细胞。作为对疫苗接种的反应，接受KGF治疗的allo-BMT受者与对照组相比，产生了更多肿瘤特异性CD8(+)细胞，以及产生干扰素-伽马(干扰素-伽马)和肿瘤坏死因子-α(TNF-α)的CD8(+)细胞数量增加。我们还发现，服用KGF对抗肿瘤免疫有意想不到的好处。KGF治疗的allo-BMT受者的T效应细胞与调节性T细胞的比率有所提高，表现为中央记忆表型的效应细胞比例更大，并且效应细胞来自更广泛的T细胞受体谱系。综上所述，我们的数据表明KGF可以通过影响移植后T细胞的重建而作为异基因骨髓移植后的一种有效的疫苗佐剂发挥作用。(血。2009；113：1574-1580)
Keratinocyte growth factor (KGF), which is given exogenously to allogeneic bone marrow transplantation (allo-BMT) recipients, supports thymic epithelial cells and increases thymic output of naive T cells. Here, we demonstrate that this improved T-cell reconstitution leads to enhanced responses to DNA plasmid tumor vaccination. Tumor-bearing mice treated with KGF and DNA vaccination have improved long-term survival and decreased tumor burden after allo-BMT. When assayed before vaccination, KGF-treated allo-BMT recipients have increased numbers of peripheral T cells, including CD8(+) T cells with vaccine-recognition potential. In response to vaccination, KGF-treated allo-BMT recipients, compared with control subjects, generate increased numbers of tumor-specific CD8(+) cells, as well as increased numbers of CD8(+) cells producing interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). We also found unanticipated benefits to antitumor immunity with the administration of KGF. KGF-treated allo-BMT recipients have an improved ratio of T effector cells to regulatory T cells, a larger fraction of effector cells that display a central memory phenotype, and effector cells that are derived from a broader T-cell-receptor repertoire. In conclusion, our data suggest that KGF can function as a potent vaccine adjuvant after allo-BMT through its effects on posttransplantation T-cell reconstitution. ( Blood. 2009; 113: 1574-1580)