Increased Survival From Stage IV Melanoma Associated With Fewer Regulatory T Cells

Background. Melanoma often elicits a profound immune response, and this response has been exploited by various immune therapies. These immunotherapies ultimately fail, however, and advanced melanoma is uniformly fatal, suggesting the development of an immune escape mechanism. In this study, markers of immune escape including regulatory T cells (T-regs), dendritic cells (DCs), and TGF-beta were evaluated in 14 Stage IV melanoma patients and correlated with survival. Materials and methods. Peripheral blood mononuclear cells were isolated from Stage IV melanoma patients and and analyzed for T-regs and DCs by flow cytometry using fluorescent CD3, CD4, CD25, Lin, HLA-DR, CD11c, and CD123 antibodies. Serum TGF-beta levels were evaluated by ELISA from these patients. Clinical data were extracted from the patients' medical records. Results. Stage TV melanoma patients with shorter survival (less than 24 mo) had a significantly higher proportion of T-regs than those with longer survival (15% versus 8%, respectively, P = 0.004). The numbers of DCs and the serum TGF-beta levels were not significantly different in these two groups. There was an inverse relationship between the percentage of T-regs and survival, although this did not reach statistical significance (r = -0.35, P = 0.22). There was also an inverse relationship between peripheral T-regs and DCs. When patients were divided into groups of greater than or less than 7% T-regs, the number of total DCs was higher in the patients with fewer T-regs than in those with more T-regs, but this did not reach statistical significance (16,535 versus 12,126 total DCs/mL, P = 0.52). Conclusions. In Stage IV melanoma patients, a high percentage of T-regs appears to be associated with shorter survival. The inverse relationship of the number of DCs and T-regs in these patients may provide an insight to the origin of this observation. (C) 2009 Elsevier Inc. All rights reserved.