Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-α 2b treatment

Paolo A. Ascierto, Maria Napolitano, Egidio Celentano, Ester Simeone, Giusy Gentilcore, Antonio Daponte, Mariaelena Capone, Corrado Caracò, Rosa Calemma, Gerardo Beneduce, Margherita Cerrone, Vincenzo De Rosa, Giuseppe Palmieri, Giuseppe Castello, John M. Kirkwood, Francesco M. Marincola, Nicola Mozzillo

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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.

Original languageEnglish
Article number76
JournalJournal of Translational Medicine
Volume8
DOIs
Publication statusPublished - 16 Aug 2010
Externally publishedYes

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interferon alfa-2b
T-cells
Regulatory T-Lymphocytes
Interferons
Melanoma
Transforming Growth Factors
Interleukin-10
Autoantibodies
Therapeutics
Serum
Recurrence
Immunosorbents
Lymphocytes
Flow cytometry

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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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 A.; Napolitano, Maria; Celentano, Egidio; Simeone, Ester; Gentilcore, Giusy; Daponte, Antonio; Capone, Mariaelena; Caracò, Corrado; Calemma, Rosa; Beneduce, Gerardo; Cerrone, Margherita; De Rosa, Vincenzo; Palmieri, Giuseppe; Castello, Giuseppe; Kirkwood, John M.; Marincola, Francesco M.; Mozzillo, Nicola.

In: Journal of Translational Medicine, Vol. 8, 76, 16.08.2010.

Research output: Contribution to journalArticle

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, JM, Marincola, FM & 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, vol. 8, 76. https://doi.org/10.1186/1479-5876-8-76
Ascierto, Paolo A. ; Napolitano, Maria ; Celentano, Egidio ; Simeone, Ester ; Gentilcore, Giusy ; Daponte, Antonio ; Capone, Mariaelena ; Caracò, Corrado ; Calemma, Rosa ; Beneduce, Gerardo ; Cerrone, Margherita ; De Rosa, Vincenzo ; Palmieri, Giuseppe ; Castello, Giuseppe ; Kirkwood, John M. ; Marincola, Francesco M. ; Mozzillo, Nicola. / Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-α 2b treatment. In: Journal of Translational Medicine. 2010 ; Vol. 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.",
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T1 - Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-α 2b treatment

AU - Ascierto, Paolo A.

AU - Napolitano, Maria

AU - Celentano, Egidio

AU - Simeone, Ester

AU - Gentilcore, Giusy

AU - Daponte, Antonio

AU - Capone, Mariaelena

AU - Caracò, Corrado

AU - Calemma, Rosa

AU - Beneduce, Gerardo

AU - Cerrone, Margherita

AU - De Rosa, Vincenzo

AU - Palmieri, Giuseppe

AU - Castello, Giuseppe

AU - Kirkwood, John M.

AU - Marincola, Francesco M.

AU - Mozzillo, Nicola

PY - 2010/8/16

Y1 - 2010/8/16

N2 - 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.

AB - 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.

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