Immunosuppressive dendritic and regulatory T cells are upregulated in melanoma patients

Ann Surg Oncol. 2007 Oct;14(10):2854-60. doi: 10.1245/s10434-007-9488-3. Epub 2007 Jun 26.


Background: Immunologic therapies for melanoma rarely succeed, suggesting a persistent counter-regulatory immune modulation. Regulatory T cells (T(regs)) and plasmacytoid subpopulations of dendritic cells (pDCs) inhibit the immune response. We hypothesize that melanoma upregulates T(regs )and subpopulations of immunosuppressive dendritic cells (DCs).

Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from healthy controls, stage I and stage IV melanoma patients. T(regs )were identified as CD4+ and CD25(hi). Dendritic cells were identified using a DC cocktail of antibodies including CD11c+ myeloid dendritic cells (mDCs) and CD123+ pDCs. Serum transforming growth factor-beta (TGF-beta), interleukin-4 (IL-4) and interleukin-10 (IL-10) levels were determined by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using analysis of variance (ANOVA).

Results: Stage IV melanoma patients had a doubling of regulatory T cells compared to both normal subjects and stage I melanoma patients. There was a significantly higher number of DCs in all melanoma patients compared to normal subjects. Stage I melanoma patients had a significantly higher number of pDCs than normal subjects, and all melanoma patients had a higher concentration of mDCs than controls. Serum IL-4 and IL-10 were not detectable but serum TGF-beta levels were significantly higher in stage I and stage IV melanoma patients compared to normal controls.

Conclusion: Advanced melanoma is associated with increased numbers of circulating dendritic cells and regulatory T cells. These data suggest that melanoma induces immunosuppressive DCs and regulatory T cells in the systemic circulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • CD4 Antigens / blood
  • Dendritic Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immune Tolerance / immunology
  • Interleukin-10 / blood
  • Interleukin-2 Receptor alpha Subunit / blood
  • Interleukin-3 Receptor alpha Subunit / blood
  • Interleukin-4 / blood
  • Lymphocyte Count
  • Male
  • Melanoma / immunology*
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Staging
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / blood
  • Tumor Escape / immunology*
  • Up-Regulation / immunology


  • CD4 Antigens
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-3 Receptor alpha Subunit
  • Transforming Growth Factor beta
  • Interleukin-10
  • Interleukin-4