Abstract
Abstract Mammaglobin-A (Mam-A), a 10kD secretory protein, is over expressed in 80% of primary and metastatic human breast cancers. Previous studies in our laboratory using a HLA-A2/Human CD8 transgenic murine model have demonstrated that Mam-A DNA Vaccine elicit specific CD8+ cytotoxic T-cell (CTL) responses to Mam-A and induces tumour regression in SCID mice. In our current study we report the activation of T-helper cells with specific expression of ICOS (inducible costimulator), a T-cell specific activation marker, following Mam-A vaccination. Stage IV breast cancer patients were chosen for the study and vaccinated by Mam-A DNA vaccine on 0, 28 and 56 days. Six months following Mam-A vaccination (n=5), flow cytometry analysis demonstrated a increase in CD4+ICOS+ T-cell frequency from 5±2% to 23± 4% with a concomitant drop in the CD4+Foxp3+T-cell (Treg) frequency from 19±6% to 10±5%. However, the frequency of CD4+CD25+ICOS+ did not change following vaccination (23±5%). ELISpot analysis demonstrated that following vaccination, CD4+ICOS+ sorted T-cells demonstrated a cytokine phenotype switch from IL-10 to IFN-γ. We conclude that following Mam-A DNA vaccination, there is a specific activation T-cells with increase in the pro-inflammatory IFN-γ CD4+ICOS+T-cells along with decrease in Treg frequency. We propose that this switch in T-cell frequency following vaccination may be important in tumor regression in breast cancer patients.
Published Version
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