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64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

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T regulatory ICOS positive and dendritic cells: Relation to WHO grade and outcome in patients with gliomas

Meeting Abstract

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  • Konstantinos Gousias - Neurochirurgische Universitätsklinik Bonn
  • Alexander von Ruecker - Institut für Pathologie, Universitätsklinikum Bonn, Bonn
  • Matthias Simon - Neurochirurgische Universitätsklinik Bonn

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocDI.09.12

doi: 10.3205/13dgnc250, urn:nbn:de:0183-13dgnc2507

Published: May 21, 2013

© 2013 Gousias et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Autologous dendritic cell (DC)-based immunotherapy has emerged as a promising novel treatment for patients with gliomas. Expression of the inducible co-stimulator (ICOS) has been recently identified as a marker for highly suppressive T regulatory cells. ICOS is an important regulator of the tumor immune escape. Little is known concerning the phenotype and prognostic relevance of T regulatory ICOS+ and DC cells in glioma patients. For the present paper we therefore correlated preoperative immunological profiles with the WHO grade and survival in glioma patients.

Method: We collected preoperative serum samples from 29 patients with cerebral gliomas and determined the phenotype of circulating T helper cells (CD4+), T regulatory cells (CD4+, CD25+, FOXP3+) and T regulatory ICOS+ cells as well as DC subsets (CD3+, CD4+, CD34+, CD45+, HLA+, DR+, Lin+/-, CD123+, CD11+, CD1c+, CD16+, CD141+) using a 6-color flow cytometry panel. Statistical analysis was performed using standard methods (i.e. Student’s t-test, Pearson's r, Kaplan-Meier, linear and cox regression).

Results: Samples from patients with glioblastomas vs. patients with gliomas WHO grade I-III contained significantly (p<0.05) decreased values (absolute counts and proportion in relation to WBC) of total as well as mature DCs, i.e. myeloid (HLA+, DR+, Lin-, CD11c+, cd123-) and plasmacytoid DCs (HLA+, DR+, Lin-, CD11c-, cd123+). Patients with glioblastomas demonstrated significantly lower values (absolute counts and proportion in relation to WBC) of CD4+ cells as well as an increased fraction of T regulatory ICOS+/ CD4+ cells. Lower counts of CD4+ cells correlated with a lesser postoperative Karnofsky index (p=0.039) and a higher rate of postoperative infections (p=0.009) in patients with glioblastomas. The fraction of mature DCs correlated inversely with the fraction of T regulatory ICOS+ /CD4+ cells (p=0.002). Higher CD4+ counts were associated with improved survival in glioblastomas in the univariate analysis (progression free survival, p=0.014).

Conclusions: Diminished values of total and mature DCs, diminished absolute counts of CD4+ as well as accumulation of highly inhibitory ICOS+ T regulatory cells may play a role in the impaired immunity observed in patients with glioblastomas. Hence, antagonizing T regulatory ICOS+ cells might be a useful addition to DC-based immunotherapy.