title: Pre-Vaccination Frequencies of Th17 Cells Correlate with Vaccine-Induced T-Cell Responses to Survivin-Derived Peptide Epitopes.
abstract: Various subsets of immune regulatory cells are suggested to influence the outcome of therapeutic antigen-specific anti-tumor vaccinations. We performed an exploratory analysis of a possible correlation of pre-vaccination Th17 cells, MDSCs, and Tregs with both vaccination-induced T-cell responses as well as clinical outcome in metastatic melanoma patients vaccinated with survivin-derived peptides. Notably, we observed dysfunctional Th1 and cytotoxic T cells, i.e. down-regulation of the CD3ζchain (p=0.001) and an impaired IFNγ-production (p=0.001) in patients compared to healthy donors, suggesting an altered activity of immune regulatory cells. Moreover, the frequencies of Th17 cells (p=0.03) and Tregs (p=0.02) were elevated as compared to healthy donors. IL-17-secreting CD4+ T cells displayed an impact on the immunological and clinical effects of vaccination: Patients characterized by high frequencies of Th17 cells at pre-vaccination were more likely to develop survivin-specific T-cell reactivity post-vaccination (p=0.03). Furthermore, the frequency of Th17 (p=0.09) and Th17/IFNγ+ (p=0.19) cells associated with patient survival after vaccination. In summary, our explorative, hypothesis-generating study demonstrated that immune regulatory cells, in particular Th17 cells, play a relevant role for generation of the vaccine-induced anti-tumor immunity in cancer patients, hence warranting further investigation to test for validity as predictive biomarkers.
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Tania
authors.initials: T
authors.lastname: Køllgaard
authors.affiliation: Department of Dermatology, University of Würzburg, Würzburg, Germany.
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel-Becker
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Manja
authors.initials: M
authors.lastname: Idorn
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
authors.affiliation: General Dermatology, Medical University of Graz, Graz, Austria.
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.affiliation: Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Per Thor
authors.initials: PT
authors.lastname: Straten
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011446:Prospective Studies; D000077022:Survivin; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
chemical_list: C107489:BIRC5 protein, human; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D019496:Cancer Vaccines; D000939:Epitopes; D051034:Inhibitor of Apoptosis Proteins; D020381:Interleukin-17; D010455:Peptides; D000077022:Survivin; D007371:Interferon-gamma