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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- Nationwide survey of malignant skin tumors (1997–2001).Skin Cancer (Japan). 2004; 19: 147-155
- Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells.Nat Med. 1998; 4: 328-332
- Vaccination of Japanese patients with advanced melanoma with peptide, tumor lysate or both peptide and tumor lysate-pulsed mature, monocyte-derived dendritic cells.J Dermatol. 2006; 33: 462-472
- Dendritic cell-based immunotherapy of malignant melanoma: success and limitations.J Dtsch Dermatol Ges. 2007; 5: 190-196
- Tumor immunity and immuno-gene therapy of malignancies.in: Mazda O. Frontiers in immuno-gene therapy. Research Signpost, Trivandrum2004: 1-30
- Circulation and homing of melanoma-reactive T cells to both cutaneous and visceral metastases after vaccination with monocyte-derived dendritic cells.Int J Cancer. 2004; 111: 229-237
- Immunohistological analysis of peptide-induced delayed-type hypersensitivity in advanced melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination.J Dermatol Sci. 2009; 53: 40-47
- Evaluation of survival in Japanese stage IV melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cells.J Dermatol. 2008; 35: 801-803
- Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients.Blood. 2006; 108: 2655-2661
- IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients.Blood. 2006; 107: 2409-2414
- Foxp3: a critical regulator of the development and function of regulatory T cells.Microbes Infect. 2004; 6: 745-751
- Toll-like receptors and immune regulation: implications for cancer therapy.Oncogene. 2008; 27: 181-189
- Local and systemic induction of CD4+CD25+ regulatory T-cell population by non-Hodgkin lymphoma.Blood. 2008; 111: 5359-5370
- CD4+CD25 high regulatory cells in peripheral blood of cancer patients.Neuro Endocrinol Lett. 2008; 29: 240-245
- Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma.J Immunol. 2002; 169: 2756-2761
- Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.Nat Med. 2004; 10: 942-949
- Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells.J Exp Med. 2003; 198: 235-247
- Effective expansion of alloantigen-specific Foxp3+ CD25+ CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction.Proc Natl Acad Sci USA. 2006; 103: 2758-2763
- Foxp3 expression on normal and leukemic CD4+CD25+ T cells implicated in human T-cell leukemia virus type-1 is inconsistent with Treg cells.Eur J Haematol. 2008; 81: 209-217
- Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B.J Immunol. 2006; 177: 739-747
- Regulatory T cells in cancer.Blood. 2006; 108: 804-811
- Peptide and dendritic cell vaccines.Clin Cancer Res. 2006; 12: 2342s-2345s
- Targeted therapies to improve tumor immunotherapy.Clin Cancer Res. 2008; 14: 4385-4391
- Improving antitumor immune responses by circumventing immunoregulatory cells and mechanisms.Clin Cancer Res. 2006; 12: 4794-4803
- Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine.Cancer Immunol Immunother. 2007; 56: 1597-1604
- Presence of low dose of fludarabine in cultures blocks regulatory T cell expansion and maintains tumor-specific cytotoxic T lymphocyte activity generated with peripheral blood lymphocytes.Pathobiology. 2008; 75: 200-208
- Comparative methodologies of regulatory T cell depletion in a murine melanoma model.J Immunol Methods. 2008; 333: 167-179
- Attenuating regulatory T cell induction by TLR agonists through inhibition of p38 MAPK signaling in dendritic cells enhances their efficacy as vaccine adjuvants and cancer immunotherapeutics.J Immunol. 2008; 180: 3797-3806
Published online: July 12, 2010
Accepted: November 22, 2008
Received in revised form: November 17, 2008
Received: August 13, 2008
© 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.