Immunosuppressive dendritic and regulatory T cells are upregulated in melanoma patients

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.