Authors: McCarter, Martin¹; Baumgartner, Joel²; Escobar, Guillermo²; Richter, Donald²; Lewis, Karl³; Robinson, William³; Wilson, Cara⁴; Palmer, Brent⁴; Gonzalez, Rene³

Source: Annals of Surgical Oncology, Volume 14, Number 10, October 2007 , pp. 2854-2860(7)

Publisher: Springer

Abstract:

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).

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-β (TGF-β), 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).

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-β levels were significantly higher in stage I and stage IV melanoma patients compared to normal controls.

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.

Keywords: Melanoma; Regulatory T cells; Dendritic cells; Immunosuppression; Human

Document Type: Research article

DOI: http://dx.doi.org/10.1245/s10434-007-9488-3

Affiliations: 1: Department of Surgery, University of Colorado at Denver Health Sciences Center, Denver, CO , 80262 , USA, Email: martin.mccarter@uchsc.edu 2: Department of Surgery, University of Colorado at Denver Health Sciences Center, Denver, CO , 80262 , USA 3: Department of Medicine, Division of Medical Oncology, University of Colorado at Denver Health Sciences Center, 4200 Ninth Avenue, C-311, Denver, CO, 80262, USA 4: Department of Medicine, Division of Immunology, University of Colorado at Denver Health Sciences Center, Denver, CO , 80262, USA

Publication date: 2007-10-01

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