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

Hongchao Cai; Yaning Feng; Peiwen Fan; Yuping Guo; Gulina Kuerban; Cheng Chang; Xuan Yao; Yanchun Peng; Ruozheng Wang

doi:10.1186/s13027-021-00395-y

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

Infect Agent Cancer. 2021 Sep 16;16(1):61. doi: 10.1186/s13027-021-00395-y.

Authors

Hongchao Cai^#^{1

2}, Yaning Feng^#^{1

2

3}, Peiwen Fan^{1

2

3}, Yuping Guo^{1

2}, Gulina Kuerban^{1

2}, Cheng Chang^{1

2}, Xuan Yao⁴, Yanchun Peng⁴, Ruozheng Wang^{5

6

7}

Affiliations

¹ The Third Affiliated Hospital of Xinjiang Medical University, Key Laboratory of Cancer Immunotherapy and Radiotherapy, Chinese Academy of Medical Sciences, Urumqi, China.
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.
⁵ The Third Affiliated Hospital of Xinjiang Medical University, Key Laboratory of Cancer Immunotherapy and Radiotherapy, Chinese Academy of Medical Sciences, Urumqi, China. wrz8526@vip.163.com.
⁶ Key Laboratory of Oncology of Xinjiang Uyghur Autonomous Region, Urumqi, China. wrz8526@vip.163.com.
⁷ State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, China. wrz8526@vip.163.com.

^# Contributed equally.

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.

Keywords: Cervical cancer; E6 and E7 peptides; HLA; Human papillomavirus 16; T cell immune response.

Abstract

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