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.
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 melanomapatients. 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 melanomapatients had a doubling of regulatory T cells compared to both normal subjects and stage I melanomapatients. There was a significantly higher number of DCs in all melanomapatients compared to normal subjects. Stage I melanomapatients had a significantly higher number of pDCs than normal subjects, and all melanomapatients 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 melanomapatients 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.
Authors: Vicky W W Tsai; Mohammad G Mohammad; Ornella Tolhurst; Samuel N Breit; Paul E Sawchenko; David A Brown Journal: J Neurosci Date: 2011-11-30 Impact factor: 6.167
Authors: Joel M Baumgartner; Kimberly R Jordan; Ling-Jia Hu; Cara C Wilson; Anirban Banerjee; Martin D McCarter Journal: J Surg Res Date: 2011-08-24 Impact factor: 2.192
Authors: Vegard Tjomsland; Per Sandström; Anna Spångeus; Davorka Messmer; Johan Emilsson; Ursula Falkmer; Sture Falkmer; Karl-Eric Magnusson; Kurt Borch; Marie Larsson Journal: BMC Cancer Date: 2010-03-09 Impact factor: 4.430