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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 10/2007

01-10-2007 | Melanomas

Immunosuppressive Dendritic and Regulatory T Cells are Upregulated in Melanoma Patients

Authors: Martin D. McCarter, MD, Joel Baumgartner, MD, Guillermo A. Escobar, MD, Donald Richter, MA, Karl Lewis, MD, William Robinson, MD, PhD, Cara Wilson, MD, Brent E. Palmer, PhD, Rene Gonzalez, MD

Published in: Annals of Surgical Oncology | Issue 10/2007

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Abstract

Background

Immunologic therapies for melanoma rarely succeed, suggesting a persistent counter-regulatory immune modulation. Regulatory T cells (Tregs) and plasmacytoid subpopulations of dendritic cells (pDCs) inhibit the immune response. We hypothesize that melanoma upregulates Tregs 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. Tregs were identified as CD4+ and CD25hi. 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).

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-β 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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Metadata
Title
Immunosuppressive Dendritic and Regulatory T Cells are Upregulated in Melanoma Patients
Authors
Martin D. McCarter, MD
Joel Baumgartner, MD
Guillermo A. Escobar, MD
Donald Richter, MA
Karl Lewis, MD
William Robinson, MD, PhD
Cara Wilson, MD
Brent E. Palmer, PhD
Rene Gonzalez, MD
Publication date
01-10-2007
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 10/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-007-9488-3

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