Pre-Vaccination Frequencies of Th17 Cells Correlate with Vaccine-Induced T-Cell Responses to Survivin-Derived Peptide Epitopes

TY - JOUR

T1 - Pre-Vaccination Frequencies of Th17 Cells Correlate with Vaccine-Induced T-Cell Responses to Survivin-Derived Peptide Epitopes

AU - Køllgaard, Tania

AU - Ugurel-Becker, Selma

AU - Idorn, Manja

AU - Andersen, Mads Hald

AU - Becker, Jürgen C

AU - thor Straten, Eivind Per

PY - 2015/7/15

Y1 - 2015/7/15

N2 - 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 IFNy- 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/IFNy+ (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 vaccineinduced anti-tumor immunity in cancer patients, hence warranting further investigation to test for validity as predictive biomarkers.

AB - 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 IFNy- 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/IFNy+ (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 vaccineinduced anti-tumor immunity in cancer patients, hence warranting further investigation to test for validity as predictive biomarkers.

KW - Adult

KW - Aged

KW - Antigens, CD3

KW - CD4-Positive T-Lymphocytes

KW - Cancer Vaccines

KW - Epitopes

KW - Humans

KW - Inhibitor of Apoptosis Proteins

KW - Interferon-gamma

KW - Interleukin-17

KW - Kaplan-Meier Estimate

KW - Leukocytes, Mononuclear

KW - Melanoma

KW - Middle Aged

KW - Neoplasm Staging

KW - Peptides

KW - Prospective Studies

KW - T-Lymphocytes, Regulatory

KW - Th17 Cells

KW - Vaccination

U2 - 10.1371/journal.pone.0131934

DO - 10.1371/journal.pone.0131934

M3 - Journal article

C2 - 26176858

SN - 1932-6203

VL - 10

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 7

M1 - e0131934

ER -