Cai Hongchao, Feng Yaning, Fan Peiwen, Guo Yuping, Kuerban Gulina, Chang Cheng, Yao Xuan, Peng Yanchun, Wang Ruozheng
The Third Affiliated Hospital of Xinjiang Medical University, Key Laboratory of Cancer Immunotherapy and Radiotherapy, Chinese Academy of Medical Sciences, Urumqi, China.
Key Laboratory of Oncology of Xinjiang Uyghur Autonomous Region, Urumqi, China.
Infect Agent Cancer. 2021 Sep 16;16(1):61. doi: 10.1186/s13027-021-00395-y.
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.
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.
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).
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.
T细胞表位是抗原呈递细胞处理后由人类白细胞抗原（HLA）基因编码的主要组织相容性复合体（MHC）分子呈递给T细胞受体的多肽片段，是研究抗原免疫机制和多表位疫苗的基础。本研究调查了宫颈鳞状细胞癌（CSCC）患者对人乳头瘤病毒16型（HPV16）E6和E7的T细胞反应。此外，还比较了患者之间的HLA - A等位基因分布，并将其评估为预测这些患者预后的一个因素。
本研究共招募了76例国际妇产科联盟（FIGO）IIB - IIIB期CSCC患者。在任何治疗前从外周血中分离单核细胞，然后采用酶联免疫斑点（ELISpot）试验检测E6和E7特异性T细胞反应。使用基于桑格测序的分型技术对外周血提取的DNA进行HLA - A等位基因分型。采用Kaplan - Meier法、单因素和多因素Cox比例风险模型分析T细胞反应、HLA - A等位基因分布与患者预后之间的相关性。
盆腔淋巴结转移患者中HPV E6特异性T细胞反应的频率低于无转移患者（P = 0.022）。对多个重叠肽有反应的患者5年总生存率（OS）为87.5%，对1 - 2个重叠肽有反应的患者为72.7%，无反应者为47.7%（P = 0.032）。Cox回归分析表明，HLA*A02:07的存在与较差的OS独立相关（风险比[HR] 3.042；95%置信区间[CI] 1.348 - 6.862；P = 0.007），而同步放化疗（CCRT）与较好的OS独立相关（HR 0.475；95% CI 0.232 - 0.975；P = 0.042）。
我们的研究结果表明，HPV16 E6特异性T细胞反应水平和HLA*A02:07与晚期CSCC患者的预后相关。
