Jianbing Ding

Bioinformatics analysis of HPV-68 E6 and E7 oncoproteins for designing a therapeutic epitope vaccine against HPV infection

The incidence and mortality of cervical cancer, which mainly results from the infection of human papillomavirus (HPV) is significantly increasing in Xinjiang. According to the previous research, the incidence of HPV-68 in cervical cancer patients in Xinjiang is significantly higher than in other parts of China. HPV E6 and E7 oncoproteins play a crucial role in cervical cancer, and can be used as ideal targets for therapeutic vaccines. Therefore, we analyzed and identified the possible T-cell and B-cell dominant epitopes and various aspects of HPV-68 E6 and E7 oncoproteins, including the physicochemical properties, secondary and tertiary structures using a bioinformatic approach, which provided a basis for designing an effective HPV infection therapeutic vaccine. The results showed that E6 oncoproteins was an unstable and hydrophilic protein, while E7 oncoproteins was unstable and hydrophilic protein. The secondary structure of the E6 oncoproteins consisted of 45.57% alpha helixes, 14.56% extended strands, 4.43% beta turns and 35.44% random coils. The secondary structure of E7 oncoproteins consisted of 35.45% alpha helixes, 17.27% extended strands, 0.91% beta turns and 46.36% random coils. Moreover, our results identified 5 dominant T-cell epitopes and 6 dominant B-cell epitopes in the E6 oncoproteins structure and 5 dominant T-cell epitopes and 3 dominant B-cell epitopes in E7 oncoproteins. In conclusion, this study provides comprehensive biological information about the HPV-68 E6 and E7 oncoproteins, which will lay a theoretical foundation for multi-epitope vaccines against HPV infection.

The role of Tim‐3/Galectin‐9 pathway in T‐cell function and prognosis of patients with human papilloma virus‐associated cervical carcinoma

Abstract The interaction between Tim‐3 on T cell and its ligand, Galectin‐9, negatively regulates cellular immune responses. However, the role of Tim‐3/Galectin‐9 pathway in the immune evasion of cervical cancer remains unknown. This study is to investigate the expression, function, and regulation of Tim‐3/Galectin‐9 signaling pathway in human papilloma virus (HPV) positive cervical cancer. Flow cytometry showed that Tim‐3 expression on T cell and Galectin‐9 expression on monocytes in HPV positive cervical cancer patients were significantly higher compared to cervical intraepithelial neoplasia and benign uterine fibroids Tim‐3 + CD4+ Th1 cells and Tim‐3 + CD8+ T cells in HPV positive cervical cancer patients were significantly reduced after surgery. Serum TGF‐β and IL‐10 levels were positively correlated with Tim‐3 + Treg cells, while IFN‐γ and IL‐2 were negatively correlated with Tim‐3 + Th1 cells. Additionally, Tim‐3 + CD4+ T cells were positively correlated with Galectin‐9 + monocytes. Survival curve analysis showed that Tim‐3 + CD4+ T cells were negatively correlated with patient survival, and closely related to FIGO stage, degree of differentiation, and lymph node metastasis of HPV positive cervical cancer. In vitro experiments showed that by blocking the Tim‐3/Galectin‐9 pathway, the proliferation of T cells and their ability to express IFN‐γ, IL‐2, perforin, and granzyme B was significantly restored. In conclusion, high levels of Tim‐3 and Galectin‐9 in HPV positive cervical cancer patients play roles in the progression of disease by promoting Treg cells to inhibit the cytotoxic function of Th1 and CD8+ T cells. Tim‐3/Galectin‐9 may serve as a new immunotherapy target for patients with HPV positive cervical cancer.