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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-α 2b treatment

Ascierto, Paolo Antonio and Napolitano, Maria and Celentano, Egidio and Simeone, Ester and Gentilcore, Giusy and Daponte, Antonio and Capone, Mariaelena and Caracò, Corrado and Calemma, Rosa and Beneduce, Gerardo and Cerrone, Margherita and De Rosa, Vincenzo and Palmieri, Giuseppe and Castello, Giuseppe and Kirkwood, John M. and Marincola, Francesco M. and Mozzillo, Nicola (2010) Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-α 2b treatment. Journal of Translational Medicine, Vol. 8 , p. 1-13. eISSN 1479-5876. Article.

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DOI: 10.1186/1479-5876-8-76

Abstract

Background: High-dose interferon-alpha 2b (IFN-α 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-α 2b by measuring serum regulatory T cell (Treg), serum transforming growth factor-β (TGF-β), interleukin (IL)-10, and autoantibody levels in patients with melanoma treated with the induction phase of the high-dose IFN-α 2b regimen.

Methods: Patients with melanoma received IFN-α 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-β, IL-10, and autoantibody levels were measured using enzyme-linked immunosorbent assays.

Results: Twenty-two patients with melanoma received IFN-α 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-α 2b treatment was observed (average decrease 0.29% per week), statistical significance was not achieved. Subgroup analyses indicated higher baseline Treg levels for stage III versus IV disease (P = 0.082), early recurrence versus no recurrence (P = 0.017), deceased versus surviving patients (P = 0.021), and preoperative neoadjuvant versus postoperative adjuvant treatment groups (not significant). No significant effects were observed on the levels of TGF-β, IL-10, and autoantibodies in patients with melanoma treated with IFN-α 2b.

Conclusions: Patients with melanoma in this study showed increased basal levels of Treg that may be relevant to their disease and its progression. Treg levels shifted in patients with melanoma treated with IFN-α 2b, although no firm conclusions regarding the role of Tregs as a marker of treatment response or outcome can be made at present.

Item Type:Article
ID Code:5372
Status:Published
Refereed:Yes
Uncontrolled Keywords:Melanoma, IFN-α 2b treatment, Treg levels
Subjects:Area 06 - Scienze mediche > MED/06 Oncologia medica
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di chimica biomolecolare, Sassari
Publisher:BioMed Central
eISSN:1479-5876
Copyright Holders:© 2010 Ascierto et al.; licensee BioMed Central Ltd.
Additional Information:This article is part of the series "Tumor Immunology and Biological Cancer Therapy", edited by iSBTc (Pedro Romero).
Deposited On:28 Jan 2011 09:39

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