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.


METHODS
Peripheral blood mononuclear cells were isolated from Stage IV melanoma patients 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 IV 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.
Baumgartner
Joel M
JM
Department of Surgery, University of Colorado Denver, Denver, Colorado 80262, USA. joel.baumgartner@uchsc.edu
Gonzalez
Rene
R
Lewis
Karl D
KD
Robinson
William A
WA
Richter
Don A
DA
Palmer
Brent E
BE
Wilson
Cara C
CC
McCarter
Martin D
MD
D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000401:mortality* / Q000473:pathology*; D015996:Survival Rate; D017741:Survivors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood
D015703:Antigens, CD; D006684:HLA-DR Antigens; D016212:Transforming Growth Factor beta