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

Authors
  • Cai, Hongchao1, 2
  • Feng, Yaning1, 2, 3
  • Fan, Peiwen1, 2, 3
  • Guo, Yuping1, 2
  • Kuerban, Gulina1, 2
  • Chang, Cheng1, 2
  • Yao, Xuan4
  • Peng, Yanchun4
  • Wang, Ruozheng1, 2, 3
  • 1 Chinese Academy of Medical Sciences,
  • 2 Key Laboratory of Oncology of Xinjiang Uyghur Autonomous Region, Urumqi, China
  • 3 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, China
  • 4 Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), Oxford, UK
Type
Published Article
Journal
Infectious Agents and Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Sep 16, 2021
Volume
16
Identifiers
DOI: 10.1186/s13027-021-00395-y
PMID: 34530896
PMCID: PMC8447512
Source
PubMed Central
Keywords
Disciplines
  • Research Article
License
Unknown

Abstract

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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