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Ann Surg Oncol. 2007 Oct;14(10):2854-60. Epub 2007 Jun 26.

Immunosuppressive dendritic and regulatory T cells are upregulated in melanoma patients.

Author information

1
Department of Surgery, University of Colorado at Denver Health Sciences Center, Denver, CO 80262, USA. martin.mccarter@uchsc.edu

Abstract

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.

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PMID:
17593331
DOI:
10.1245/s10434-007-9488-3
[Indexed for MEDLINE]

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