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HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer

BACKGROUND: T cell epitopes are polypeptide fragments presented to T cell receptors by MHC molecules encoded by human leukocyte antigen (HLA) genes after antigen-presenting cell processing, which is the basis for the study of antigen immune mechanism and multi-epitope vaccine. This study investigate...

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Autores principales: Cai, Hongchao, Feng, Yaning, Fan, Peiwen, Guo, Yuping, Kuerban, Gulina, Chang, Cheng, Yao, Xuan, Peng, Yanchun, Wang, Ruozheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447512/
https://www.ncbi.nlm.nih.gov/pubmed/34530896
http://dx.doi.org/10.1186/s13027-021-00395-y
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author Cai, Hongchao
Feng, Yaning
Fan, Peiwen
Guo, Yuping
Kuerban, Gulina
Chang, Cheng
Yao, Xuan
Peng, Yanchun
Wang, Ruozheng
author_facet Cai, Hongchao
Feng, Yaning
Fan, Peiwen
Guo, Yuping
Kuerban, Gulina
Chang, Cheng
Yao, Xuan
Peng, Yanchun
Wang, Ruozheng
author_sort Cai, Hongchao
collection PubMed
description BACKGROUND: T cell epitopes are polypeptide fragments presented to T cell receptors by MHC molecules encoded by human leukocyte antigen (HLA) genes after antigen-presenting cell processing, which is the basis for the study of antigen immune mechanism and multi-epitope vaccine. This study investigated T cell response to HPV16 E6 and E7 in patients with cervical squamous cell carcinoma (CSCC). Also, the HLA-A allele distribution was compared among patients and evaluated as a factor to predict prognosis in these patients. MATERIALS AND METHODS: This study recruited a total of 76 patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IIIB CSCC. Mononuclear cells were isolated from the peripheral blood before any treatment and then enzyme-linked immunosorbent spot (ELISpot) assay was employed to measure the E6 and E7-specific T cell response. HLA‐A alleles were typed using Sanger sequencing‐based typing techniques with DNA extracted from the peripheral blood. The correlation between the T cell responses, HLA‐A allele distribution and patient prognosis were analysed using the Kaplan–Meier method, univariate and multivariate Cox proportional hazard models. RESULTS: The frequency of HPV E6-specific T cell responses in patients with pelvic lymph node metastasis was lower than that in patients without metastasis (P = 0.022). The 5-year overall survival (OS) rates of patients were 87.5% for those responding to multiple overlapping peptides, 72.7% for those responding to 1–2 overlapping peptides and 47.7% for non-responders (P = 0.032). Cox regression analysis indicated that the presence of HLA*A02:07 was independently associated with worse OS (hazard ratio [HR] 3.042; 95% confidence interval [CI] 1.348–6.862; P = 0.007), while concurrent chemoradiation therapy (CCRT) was independently associated with better OS (HR 0.475; 95% CI 0.232–0.975; P = 0.042). CONCLUSION: The results of our study demonstrated that the level of HPV16 E6-specific T cell response and HLA*A02:07 were correlated with prognosis in patients with advanced CSCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13027-021-00395-y.
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spelling pubmed-84475122021-09-17 HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer Cai, Hongchao Feng, Yaning Fan, Peiwen Guo, Yuping Kuerban, Gulina Chang, Cheng Yao, Xuan Peng, Yanchun Wang, Ruozheng Infect Agent Cancer Research Article BACKGROUND: T cell epitopes are polypeptide fragments presented to T cell receptors by MHC molecules encoded by human leukocyte antigen (HLA) genes after antigen-presenting cell processing, which is the basis for the study of antigen immune mechanism and multi-epitope vaccine. This study investigated T cell response to HPV16 E6 and E7 in patients with cervical squamous cell carcinoma (CSCC). Also, the HLA-A allele distribution was compared among patients and evaluated as a factor to predict prognosis in these patients. MATERIALS AND METHODS: This study recruited a total of 76 patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IIIB CSCC. Mononuclear cells were isolated from the peripheral blood before any treatment and then enzyme-linked immunosorbent spot (ELISpot) assay was employed to measure the E6 and E7-specific T cell response. HLA‐A alleles were typed using Sanger sequencing‐based typing techniques with DNA extracted from the peripheral blood. The correlation between the T cell responses, HLA‐A allele distribution and patient prognosis were analysed using the Kaplan–Meier method, univariate and multivariate Cox proportional hazard models. RESULTS: The frequency of HPV E6-specific T cell responses in patients with pelvic lymph node metastasis was lower than that in patients without metastasis (P = 0.022). The 5-year overall survival (OS) rates of patients were 87.5% for those responding to multiple overlapping peptides, 72.7% for those responding to 1–2 overlapping peptides and 47.7% for non-responders (P = 0.032). Cox regression analysis indicated that the presence of HLA*A02:07 was independently associated with worse OS (hazard ratio [HR] 3.042; 95% confidence interval [CI] 1.348–6.862; P = 0.007), while concurrent chemoradiation therapy (CCRT) was independently associated with better OS (HR 0.475; 95% CI 0.232–0.975; P = 0.042). CONCLUSION: The results of our study demonstrated that the level of HPV16 E6-specific T cell response and HLA*A02:07 were correlated with prognosis in patients with advanced CSCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13027-021-00395-y. BioMed Central 2021-09-16 /pmc/articles/PMC8447512/ /pubmed/34530896 http://dx.doi.org/10.1186/s13027-021-00395-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Cai, Hongchao
Feng, Yaning
Fan, Peiwen
Guo, Yuping
Kuerban, Gulina
Chang, Cheng
Yao, Xuan
Peng, Yanchun
Wang, Ruozheng
HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer
title HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer
title_full HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer
title_fullStr HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer
title_full_unstemmed HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer
title_short HPV16 E6-specific T cell response and HLA-A alleles are related to the prognosis of patients with cervical cancer
title_sort hpv16 e6-specific t cell response and hla-a alleles are related to the prognosis of patients with cervical cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447512/
https://www.ncbi.nlm.nih.gov/pubmed/34530896
http://dx.doi.org/10.1186/s13027-021-00395-y
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