Vaccination Against Human Papilloma Viruses Leads to a Favorable Cytokine Profile of Specific T Cells
Vaccination Against Human Papilloma Viruses Leads to a Favorable Cytokine Profile of Specific T Cells
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DOI：
10.1097/cji.0000000000000137
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发表时间：
2016-10-01
影响因子：
3.9
通讯作者：
Lindemann, Monika
中科院分区：
文献类型：
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作者：
Luckau, Stefanie;Wehrs, Tim P.;Lindemann, Monika
已知几种人类乳头瘤病毒（HPV）可引起恶性转化。高危型HPV 16与宫颈癌和头颈部鳞状细胞癌有关。HPV 16阳性肿瘤细胞只携带HPV 16致癌基因E6和E7。这些癌基因似乎是过继免疫治疗的极佳靶点。我们在这里讨论了hpv疫苗接种的健康志愿者的特异性T细胞是否特别适合hpv特异性细胞免疫治疗的问题。值得注意的是，疫苗含有HPV 16。为了量化HPV 16 e6特异性和e7特异性细胞，优化了酶联免疫斑点法测定干扰素- γ (ifn - γ)和白介素-10 （Th1-Th2平衡）以及细胞内分子颗粒酶B和穿孔素的分泌。与未接种hpv疫苗的志愿者相比，接种hpv疫苗的志愿者外周血单核细胞分泌ifn - γ和穿孔素的频率显著（P < 0.05）增加。然而，总体而言，即使在接种疫苗的志愿者中，具有良好分泌谱（Th1平衡和细胞毒性）的HPV 16特异性细胞的中位数频率也很低（e6特异性和e7特异性细胞的ifn - γ分别为0.0018%和0.0023%，穿孔素分别为0.01%和0.0087%）。但一些接种疫苗的志愿者显示出高达0.1%的hpv特异性、ifn - γ或穿孔素分泌细胞。总之，我们的数据表明，接种疫苗的志愿者在hpv特异性细胞癌免疫治疗方面优于未接种疫苗的供体。
Several human papilloma viruses (HPV) are known to cause malignant transformation. The high-risk type HPV 16 is associated with cervical carcinoma and head and neck squamous cell carcinoma. HPV 16-positive tumor cells exclusively carry the HPV 16 oncogenes E6 and E7. These oncogenes appear as excellent targets for an adoptive immunotherapy. We here addressed the question whether specific T cells from HPV-vaccinated healthy volunteers could be especially suitable for an HPV-specific cellular immunotherapy. Of note, vaccines contain HPV 16. To quantify HPV 16 E6-specific and E7-specific cells, enzyme-linked immunospot assays to measure interferon-gamma (IFN-gamma) and interleuldn-10 (Th1-Th2 balance) and the secretion of the cytotcaic molecules granzyme B and perforin have been optimized. The frequency of peripheral blood mononuclear cells secreting IFN-gamma and perforin was significantly (P < 0.05) increased in HPV-vaccinated versus nonvaccinated volunteers. Overall, however, the median frequency of HPV 16-specific cells with a favorable secretion profile (Th1 balanced and cytotoxic) was low even in vaccinated volunteers (IFN-gamma: 0.0018% and 0.0023%, perforin: 0.01% and 0.0087% for E6-specific and E7-specific cells, respectively). But some vaccinated volunteers showed up to 0.1% HPV-specific, IFN-gamma or perforin-secreting cells. In conclusion, our data suggest that vaccinated volunteers are superior to nonvaccinated donors for HPV-specific cellular cancer immunotherapy.