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Immunosuppressive Dendritic and Regulatory T Cells are Upregulated in Melanoma Patients

  • Melanomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Acknowledgments

This work supported in part by a 5 K12 CA86913 clinical oncology research career-development program award.

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Authors and Affiliations

  1. Department of Surgery, University of Colorado at Denver Health Sciences Center, Denver, CO , 80262 , USA

    Martin D. McCarter MD, Joel Baumgartner MD, Guillermo A. Escobar MD & Donald Richter MA

  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

    Karl Lewis MD, William Robinson MD, PhD & Rene Gonzalez MD

  3. Department of Medicine, Division of Immunology, University of Colorado at Denver Health Sciences Center, Denver, CO , 80262, USA

    Cara Wilson MD & Brent E. Palmer PhD

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  1. Martin D. McCarter MD
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  2. Joel Baumgartner MD
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Correspondence to Martin D. McCarter MD.

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McCarter, M.D., Baumgartner, J., Escobar, G.A. et al. Immunosuppressive Dendritic and Regulatory T Cells are Upregulated in Melanoma Patients. Ann Surg Oncol 14, 2854–2860 (2007). https://doi.org/10.1245/s10434-007-9488-3

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  • DOI: https://doi.org/10.1245/s10434-007-9488-3

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