Mapping of HPV-specific CD8 T cells and immune signature in cervical intraepithelial neoplasia and cancer 3635

Abstract Description The development of cervical cancer is driven by persistent HPV infection and the oncogenic activity of viral proteins E6 and E7. The disease progresses from cervical intraepithelial neoplasia (CIN) to invasive cancer. While most individuals clear HPV infections, some cannot mount an adequate immune response leading to cervical cancer (CC). This study aimed to map HPV-specific CD8 T-cell recognition and characterize immune signatures in CIN and cancer. We performed high-throughput screening of HPV-specific CD8 T-cells using DNA barcode-labelled peptide-MHC multimers and immunophenotyped cells in cervical samples and PBMCs from healthy donors, CIN3, and CC patients. Our results suggested impaired HPV-specific CD8 T-cell response in cancer patients. Additionally, we identified a large proportion of tumor-infiltrating CD8 T-cells exhibiting late activation/exhaustion in cervical cancer patients, which correlated with cancer stage. The immunosuppressive tumor microenvironment was characterized by a higher percentage of Tregs and PDL-1 expression by myeloid cells. These characteristics were mainly observed in cancer patients’ cervical samples, with no significant transcriptomic differences between healthy individuals and CIN3 patients. Our findings indicate that cervical cancer patients elicit an ongoing but impaired immune response toward the tumor, raising a terminally differentiated CD8 T-cell response toward HPV, which might be relevant for future immunotherapy. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)