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Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-a 2b treatment | Ascierto et al. Journal of Translational Medicine 2010 8 76 http www.translational-medicine.eom content 8 1 76 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Regulatory T cell frequency in patients with melanoma with different disease stage and course and modulating effects of high-dose interferon-a 2b treatment 1 1 1 1 1 1 Paolo A Ascierto Maria Napolitano Egidio Celentano Ester Simeone Giusy Gentilcore Antonio Daponte 1 r- I z- 1 1 1 1 Mariaelena Capone Corrado Caracò Rosa Calemma Gerardo Beneduce Margherita Cerrone inr Qn7 i rio Dr icsC fCii iconno Dtỉ Imiori2 ii TỉctollrC M ICirlztA r ir iH2 K l K r i n t I 4 Vincenzo De Rosa Giuseppe Palmieri Giuseppe Castello John M Kirkwood Francesco M Marincola Nicola Mozzillo 1 Abstract Background High-dose interferon-alpha 2b IFN-a 2b is the only approved systemic therapy in the United States for the adjuvant treatment of melanoma. The study objective was to explore the immunomodulatory mechanism of action for IFN-a 2b by measuring serum regulatory T cell Treg serum transforming growth factor-p TGF-P interleukin IL -10 and autoantibody levels in patients with melanoma treated with the induction phase of the high-dose IFN-a 2b regimen. Methods Patients with melanoma received IFN-a 2b administered intravenously 20 MU m2 each day from day 1 to day 5 for 4 consecutive weeks . Serum Treg levels were measured as whole lymphocytes in CD4 cells using flow cytometry while TGF-p IL-10 and autoantibody levels were measured using enzyme-linked immunosorbent assays. Results Twenty-two patients with melanoma received IFN-a 2b treatment and were evaluated for Treg levels. Before treatment Treg levels were significantly higher in patients with melanoma when compared with data from 20 healthy subjects P 0.001 Mann-Whitney test . Although a trend for reduction of Treg levels following IFN-a 2b treatment was observed average decrease 0.29 per week statistical significance was not achieved. Subgroup analyses indicated higher baseline
