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Immunosuppressive Dendritic and Regulatory T Cells are Upregulated in Melanoma Patients

¹ Department of Surgery, University of Colorado at Denver Health Sciences Center, Denver, CO 80262, USA
² Department of Medicine, Division of Medical Oncology, University of Colorado at Denver Health Sciences Center, 4200 Ninth Avenue, C-311, Denver, CO 80262, USA
³ Department of Medicine, Division of Immunology, University of Colorado at Denver Health Sciences Center, Denver, CO 80262, USA

Correspondence: Address correspondence and reprint requests to: Martin D. McCarter, MD; E-mail: martin.mccarter{at}uchsc.edu

Background: Immunologic therapies for melanoma rarely succeed, suggesting a persistent counter-regulatory immune modulation. Regulatory T cells (T_regs) and plasmacytoid sub-populations 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-ß (TGF-ß), 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-ß 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.

Key Words: Melanoma • Regulatory T cells • Dendritic cells • Immunosuppression • Human

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