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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, PA and Napolitano, M and Celentano, E and Simeone, E and Gentilcore, G and Daponte, A and Capone, M and Caracò, C and Calemma, R and Beneduce, G and Cerrone, M and De Rosa, V and Palmieri, G and Castello, G and Kirkwood, JM and Marincola, FM and Mozzillo, N (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, 8.

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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. © 2010 Ascierto et al; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ascierto, PA
Napolitano, M
Celentano, E
Simeone, E
Gentilcore, G
Daponte, A
Capone, M
Caracò, C
Calemma, R
Beneduce, G
Cerrone, M
De Rosa, V
Palmieri, G
Castello, G
Kirkwood, JMkirkwood@pitt.eduKIRKWOOD
Marincola, FM
Mozzillo, N
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 16 August 2010
Date Type: Publication
Journal or Publication Title: Journal of Translational Medicine
Volume: 8
DOI or Unique Handle: 10.1186/1479-5876-8-76
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Date Deposited: 14 Nov 2016 16:57
Last Modified: 04 Feb 2019 15:56
URI: http://d-scholarship.pitt.edu/id/eprint/30246

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