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Indoleamine 2,3-dioxygenase, a new prognostic marker in sentinel lymph nodes of melanoma patients.

AbstractBACKGROUND:
Indoleamine 2,3-dioxygenase (IDO), an enzyme with immunosuppressive properties is considered as a factor that impairs the antitumour immune response in melanoma. In this study, we investigated the expression of IDO in sentinel nodes of melanoma patients to determine its prognostic relevance.
PATIENTS AND METHODS:
One hundred and sixteen melanoma patients were enrolled in this study with a median follow-up time after diagnosis of 71 months. The expression of IDO and forkhead box P3 (Foxp3) in the sentinel lymph nodes was determined by immunohistochemistry and correlated with progression-free survival and overall survival. In 42 patients, regulatory T cells were investigated by flow cytometry.
RESULTS:
Cox regression survival analysis showed a significant negative effect of IDO expression on progression-free survival (p = 0.015) and overall survival (p = 0.010). High IDO expression was correlated with a significant higher frequency of Foxp3-positive cells in uninvaded lymph nodes (p = 0.016). The presence of IDO expression in the sentinel nodes was not associated with an increased frequency of circulating regulatory T cells (Tregs) but was significantly correlated with an increased mean fluorescence intensity of Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) in Tregs (p = 0.019). After CD3CD28 stimulation, peripheral blood mononuclear cells of patients with high IDO expression showed a lower production of interferon-gamma (IFN-γ) (p = 0.025).
CONCLUSIONS:
This study points to an independent predictive role of IDO on survival, especially in melanoma patients with uninvolved sentinel nodes. Investigating IDO expression in the sentinel nodes of melanoma patients may be a useful marker to pre-identify patients with a less favourable prognosis in stage I and II disease.
AuthorsReinhart Speeckaert, Karim Vermaelen, Nanja van Geel, Philippe Autier, Jo Lambert, Marc Haspeslagh, Mireille van Gele, Kris Thielemans, Bart Neyns, Nathalie Roche, Natacha Verbeke, Philippe Deron, Marijn Speeckaert, Lieve Brochez
JournalEuropean journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 48 Issue 13 Pg. 2004-11 (Sep 2012) ISSN: 1879-0852 [Electronic] England
PMID22033321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • CTLA-4 Antigen
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-gamma
Topics
  • Adult
  • CTLA-4 Antigen (metabolism)
  • Female
  • Forkhead Transcription Factors (metabolism)
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase (metabolism)
  • Interferon-gamma (metabolism)
  • Leukocytes, Mononuclear (immunology)
  • Lymph Nodes (metabolism)
  • Lymphatic Metastasis
  • Male
  • Melanoma (diagnosis, mortality)
  • Middle Aged
  • Prognosis
  • Sentinel Lymph Node Biopsy
  • Skin Neoplasms (diagnosis, mortality)
  • T-Lymphocytes, Regulatory (immunology)

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