title: Vaccination Against Human Papilloma Viruses Leads to a Favorable Cytokine Profile of Specific T Cells.
abstract: Several human papilloma viruses (HPV) are known to cause malignant transformation. The high-risk type HPV 16 is associated with cervical carcinoma and head and neck squamous cell carcinoma. HPV 16-positive tumor cells exclusively carry the HPV 16 oncogenes E6 and E7. These oncogenes appear as excellent targets for an adoptive immunotherapy. We here addressed the question whether specific T cells from HPV-vaccinated healthy volunteers could be especially suitable for an HPV-specific cellular immunotherapy. Of note, vaccines contain HPV 16. To quantify HPV 16 E6-specific and E7-specific cells, enzyme-linked immunospot assays to measure interferon-γ (IFN-γ) and interleukin-10 (Th1-Th2 balance) and the secretion of the cytotoxic molecules granzyme B and perforin have been optimized. The frequency of peripheral blood mononuclear cells secreting IFN-γ and perforin was significantly (P<0.05) increased in HPV-vaccinated versus nonvaccinated volunteers. Overall, however, the median frequency of HPV 16-specific cells with a favorable secretion profile (Th1 balanced and cytotoxic) was low even in vaccinated volunteers (IFN-γ: 0.0018% and 0.0023%, perforin: 0.01% and 0.0087% for E6-specific and E7-specific cells, respectively). But some vaccinated volunteers showed up to 0.1% HPV-specific, IFN-γ or perforin-secreting cells. In conclusion, our data suggest that vaccinated volunteers are superior to nonvaccinated donors for HPV-specific cellular cancer immunotherapy.
authors.affiliation: *Institute for Transfusion Medicine †Department of Otorhinolaryngology, University Hospital, Essen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Luckau
authors.forename: Tim P
authors.initials: TP
authors.lastname: Wehrs
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
authors.forename: Peter A
authors.initials: PA
authors.lastname: Horn
authors.forename: Monika
authors.initials: M
authors.lastname: Lindemann
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000628:therapy*; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology / Q000628:therapy*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D054353:Perforin / Q000378:metabolism; D012097:Repressor Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy*; D014611:Vaccination
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D054353:Perforin; D016753:Interleukin-10; D007371:Interferon-gamma; D053804:Granzymes