Immunosuppressive Dendritic and Regulatory T Cells are Upregulated in Melanoma Patients Export

@article{citeulike:3725336, abstract = {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.}, author = {Mccarter, Martin and Baumgartner, Joel and Escobar, Guillermo and Richter, Donald and Lewis, Karl and Robinson, William and Wilson, Cara and Palmer, Brent and Gonzalez, Rene}, citeulike-article-id = {3725336}, citeulike-linkout-0 = {http://dx.doi.org/10.1245/s10434-007-9488-3}, citeulike-linkout-1 = {http://www.springerlink.com/content/k0gk8740u3n75744}, day = {1}, doi = {10.1245/s10434-007-9488-3}, journal = {Annals of Surgical Oncology}, keywords = {dendritic, immune-supression, melanoma, new-direction, treg, treg-background}, month = {October}, number = {10}, pages = {2854--2860}, posted-at = {2008-11-29 03:46:02}, priority = {2}, title = {Immunosuppressive Dendritic and Regulatory T Cells are Upregulated in Melanoma Patients}, url = {http://dx.doi.org/10.1245/s10434-007-9488-3}, volume = {14}, year = {2007} }

TY - JOUR ID - citeulike:3725336 L3 - citeulike-article-id:3725336 N2 - 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. IS - 10 JF - Annals of Surgical Oncology EP - 2860 TI - Immunosuppressive Dendritic and Regulatory T Cells are Upregulated in Melanoma Patients VL - 14 SP - 2854 KW - dendritic KW - immune-supression KW - melanoma KW - new-direction KW - treg KW - treg-background AU - Mccarter, Martin AU - Baumgartner, Joel AU - Escobar, Guillermo AU - Richter, Donald AU - Lewis, Karl AU - Robinson, William AU - Wilson, Cara AU - Palmer, Brent AU - Gonzalez, Rene PY - 2007/10/01/ UR - http://dx.doi.org/10.1245/s10434-007-9488-3 ER -