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

• Published in: Infectious agents and cancer Vol. 16; no. 1; pp. 1 - 61
• Main Authors: Cai, Hongchao, Feng, Yaning, Fan, Peiwen, Guo, Yuping, Kuerban, Gulina, Chang, Cheng, Yao, Xuan, Peng, Yanchun, Wang, Ruozheng
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 16.09.2021; BioMed Central; BMC
• Subjects: Alleles; Allelomorphism; Antigen-presenting cells; Antigenic determinants; Cancer therapies; Cervical cancer; Chemoradiotherapy; Chemotherapy; Comparative analysis; Disease; DNA sequencing; E6 and E7 peptides; Enzyme-linked immunosorbent assay; Enzymes; Epitopes; Histocompatibility antigen HLA; Histocompatibility antigens; HLA; HLA histocompatibility antigens; Human papillomavirus; Human papillomavirus 16; Immunotherapy; Infections; Leukocytes (mononuclear); Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Medical prognosis; Medical research; Medicine, Experimental; Metastases; Metastasis; Mutation; Nucleotide sequencing; Obstetrics; Papillomavirus infections; Patients; Peptides; Peripheral blood; Prognosis; Proteins; Radiation therapy; Squamous cell carcinoma; Survival analysis; T cell immune response; T cells; Tissue typing; Vaccines; Australia; United States > US
• ISSN: 1750-9378; 1750-9378
• DOI: 10.1186/s13027-021-00395-y

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.