scholarly journals Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed

2021 ◽  
Vol 12 ◽  
Author(s):  
Takeo Shibata ◽  
Sumit Shah ◽  
Teresa Evans ◽  
Hannah Coleman ◽  
Benjamin J. Lieblong ◽  
...  

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.

2020 ◽  
Author(s):  
Takeo Shibata ◽  
Sumit Shah ◽  
Teresa Evans ◽  
Hannah Coleman ◽  
Benjamin J. Lieblong ◽  
...  

AbstractAdvances 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. Interferon-γ enzyme-linked immunospot assay identified significantly increased HPV-specific T cell response in the HPV 16 E6 91-115 region after 4 vaccinations (p=0.023). T cells with specificity to this region 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 in the periphery and cervix.


2014 ◽  
Vol 134 (3) ◽  
pp. 534-539 ◽  
Author(s):  
Adela Carrillo-García ◽  
Sergio Ponce-de-León-Rosales ◽  
David Cantú-de-León ◽  
Verónica Fragoso-Ontiveros ◽  
Imelda Martínez-Ramírez ◽  
...  

2021 ◽  
Author(s):  
Burak Sezgin ◽  
Fatih Pirinççi ◽  
Aysun Camuzcuoğlu ◽  
Eda Adeviye Şahin ◽  
Özcan Erel ◽  
...  

Abstract Purpose: This study aimed to determine the potential clinical use of dynamic thiol disulfide balance in cases with preinvasive lesions of the cervix.Methods: One hundred and sixteen patients with high-grade squamous intraepithelial lesion, one hundred patients with low-grade squamous intraepithelial lesion and one hundred and ten healthy controls were enrolled in the study. A fully automated colorimetric system was used to determine the levels of thiol-disulfide parameters. The ischemia-modified albumin, total oxidant-antioxidant capacity, oxidative stress index of the retrieved cases were further analysed.Results: Native thiol and total thiol levels are significantly lower in the high-grade squamous intraepithelial lesion group according to control group (p:0.004 and p:0.015, respectively). Disulfide level is significantly increased in the high-grade squamous intraepithelial lesion group compared to control group (p:0.004). Oxidative stress index levels in high-grade squamous intraepithelial lesion group were observed as significantly higher according to the control group (p:0.014). Ischemia-modified albumin levels in the high-grade squamous intraepithelial lesion group were observed as significantly higher compared to the control group (p:0.020). Disulfide levels are positively correlated with risk type of Human papillomavirus (r:0.420, p<0.001).Conclusion: The analysis of dynamic thiol disulfide balance revealed considerable oxidative damage in patients with Human papillomavirus -related cervical precursor lesions compared to women with ordinary cytology specimens. Therefore, investigation of thiol disulfide balance with presented method represents a new promising test for early diagnosis and management of women at high risk for cervical cancer.


2019 ◽  
Vol 152 (3) ◽  
pp. 359-364
Author(s):  
Edward B Stelow ◽  
Erik A Dill ◽  
Jonathan J Davick ◽  
Michael B McCabe ◽  
Vanessa M Shami

ABSTRACT Objectives Although the role of human papillomavirus (HPV) in the development of some carcinomas (eg, anogenital and oropharyngeal squamous cell carcinomas) is nondebatable, there is still significant controversy regarding the relationship of HPV and esophageal squamous cell carcinomas (SCCs). Methods All cases were sampled at or near the gastroesophageal junctions in patients with reflux and/or known Barrett esophagus and appear to have been initially sampled “incidentally.” Patients were all men, aged 56 to 80 years. None had a known history of other HPV-related disease. Results We present four cases of high-grade squamous intraepithelial lesion of the gastroesophageal junction secondary to high-risk HPV that have identical histologic features to similar lesions of the anogenital tract. Conclusions Whether such lesions are at risk for developing into invasive SCC remains unclear.


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