Immunoregulatory T cells in the peripheral blood of melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination.
ABSTRACT Regulatory T cells (Treg) may inhibit monocyte-derived melanoma antigen-pulsed dendritic cells (DC) vaccination in treatment of melanoma. However, the Treg level in peripheral blood mononuclear cells (PBMCs) following DC vaccination has not been examined in melanoma patients in Japan.
To evaluate differences in the helper T cell and Treg population and mRNA levels of Treg in pre- and post-DC vaccination PBMCs obtained from melanoma patients.
Levels of intracellular forkhead box protein 3 (Foxp3) mRNA as well as levels of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(+) T cells were examined by real-time PCR and flow cytometry using PBMCs from 9 patients who received DC vaccination.
Eight of the 9 cases and 7 of the 9 cases showed increased populations of CD4(+)CD25(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells, respectively after repeated DC vaccination. Five of 8 cases showed an increase of Foxp3 mRNA after treatment. Four of these 5 cases also had increased CD4(+)CD25(+) and CD4(+)CD25(+)Foxp3(+) T cells, but the fifth case showed a decrease in CD4(+)CD25(+)Foxp3(+) T cells. Three cases showed a decrease of Foxp3 mRNA. One of these 3 cases showed decreased population of CD4(+)CD25(+)Foxp3(+) T cells, but two cases showed increased population of CD4(+)CD25(+)Foxp3(+) T cells. In 3 of 8 cases Foxp3 expression at the cellular (protein) and mRNA level were inconsistent.
Repeated DC vaccination may commonly induce Treg and helper T cells at the cellular level. However, there are a few discrepancies of Treg expression at cellular and mRNA level.
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ABSTRACT: Induction of tumor-specific immunity is an attractive approach to cancer therapy, however to date every major pivotal trial has resulted in failure. While the phenomena of tumor-mediated immune suppression has been known for decades, only recently have specific molecular pathways been elucidated, and for the first time, rationale means of intervening and observing results of intervention have been developed. In this review we describe major advances in our understanding of tumor escape from immunological pressure and provide some possible therapeutic scenarios for enhancement of efficacy in future cancer vaccine trials.Cellular Immunology 01/2010; 263(2):138-47. · 1.97 Impact Factor