Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed.
Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed.
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DOI：
10.3389/fimmu.2021.645299
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发表时间：
2021
影响因子：
7.3
通讯作者：
Nakagawa M
中科院分区：
文献类型：
--
作者：
Shibata T;Shah S;Evans T;Coleman H;Lieblong BJ;Spencer HJ;Quick CM;Sasagawa T;Stephens OW;Peterson E;Johann D Jr;Lu YC;Nakagawa M
高通量测序的进展彻底改变了我们研究T细胞反应的方式。我们描述了一名妇女谁收到了人乳头瘤病毒（HPV）治疗性疫苗称为PepCan，并经历了她的宫颈高度鳞状上皮内病变完全解决。通过在4次疫苗接种之前和之后对外周血单核细胞进行批量T细胞受体（TCR）β深度测序，使用β-二项式模型鉴定出70种脓毒疫苗特异性克隆型显著增加。为了验证这些克隆型的疫苗特异性，使用单细胞RNA-seq和TCR测序分选并分析对HPV 16 E6 91-115区域具有特异性的T细胞，该区域先前使用干扰素-γ酶联免疫斑点测定法鉴定为疫苗诱导的。HPV特异性在60的70个克隆型被确定为疫苗特异性证明。在4次疫苗接种前后，宫颈液基细胞学样本和宫颈福尔马林固定石蜡包埋样本的TCR β批量测序证实了这些HPV特异性T细胞在宫颈中的存在。结合传统和尖端的免疫监测技术，使我们能够证明HPV抗原特异性T细胞不仅在外周而且在宫颈中的扩增。这种方法应该是有用的，作为一种新的方法来评估疫苗特异性反应在不同的解剖区域。
Advances in high-throughput sequencing have revolutionized the manner with which we can study T cell responses. We describe a woman who received a human papillomavirus (HPV) therapeutic vaccine called PepCan, and experienced complete resolution of her cervical high-grade squamous intraepithelial lesion. By performing bulk T cell receptor (TCR) β deep sequencing of peripheral blood mononuclear cells before and after 4 vaccinations, 70 putatively vaccine-specific clonotypes were identified for being significantly increased using a beta-binomial model. In order to verify the vaccine-specificity of these clonotypes, T cells with specificity to a region, HPV 16 E6 91-115, previously identified to be vaccine-induced using an interferon-γ enzyme-linked immunospot assay, were sorted and analyzed using single-cell RNA-seq and TCR sequencing. HPV specificity in 60 of the 70 clonotypes identified to be vaccine-specific was demonstrated. TCR β bulk sequencing of the cervical liquid-based cytology samples and cervical formalin-fixed paraffin-embedded samples before and after 4 vaccinations demonstrated the presence of these HPV-specific T cells in the cervix. Combining traditional and cutting-edge immunomonitoring techniques enabled us to demonstrate expansion of HPV-antigen specific T cells not only in the periphery but also in the cervix. Such an approach should be useful as a novel approach to assess vaccine-specific responses in various anatomical areas.
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影响因子：
2.1
作者：
Garolla, Andrea;Pizzol, Damiano;Foresta, Carlo
通讯作者：
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作者：
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