gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

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Immune escape of malignant glioma: Interference with dendritic cell mediated immunity

Immune escape Mechanismen maligner Gliome und ihre Interferenz mit dendritischen Zellen

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  • corresponding author M. Rapp - Neurochirurgische Klinik, Universität Düsseldorf
  • T. Beetz - Neurochirurgische Klinik, Universität Düsseldorf
  • Z. Özcan - Institut für Transplantationsdiagnostik und Zelltherapeutika, Universität Düsseldorf
  • S. De Vleeschouwer - Neurochirurgische Klinik, Universität Düsseldorf
  • H.J. Steiger - Neurochirurgische Klinik, Universität Düsseldorf
  • P. Wernet - Institut für Transplantationsdiagnostik und Zelltherapeutika, Universität Düsseldorf
  • R.V. Sorg - Institut für Transplantationsdiagnostik und Zelltherapeutika, Universität Düsseldorf
  • M. Sabel - Neurochirurgische Klinik, Universität Düsseldorf

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 05.64

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2006/06dgnc281.shtml

Published: May 8, 2006

© 2006 Rapp 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: Dendritic cells (DC) are antigen-presenting cells pivotal to anti-tumor immunity, due to their central role in the initiation phase of T-cell responses. Therefore, they represent a potential target for immune escape strategies of tumors. To identify such mechanisms of immune evasion of glioma cells, interference of the cell lines U373 and A172 with DC differentiation, maturation and function was studied.

Methods: Immunomagnetically enriched monocytes were cultured under serum-free conditions in the presence or absence of glioma conditioned medium (CM) with GM-CSF and IL-4 for 6 days, to induced immature DC differentiation, followed by an additional 3-day culture period with GM-CSF, IL-4 and TNFα, to induce DC maturation. Differentiation/maturation was monitored by flow cytometry. Functional characterization of immature and mature DC involved determination of antigen-uptake activity and T-cell stimulatory activity for proliferative and cytokine responses, respectively.

Results: Immature DC showed mainly a CD14-/CD83- phenotype and revealed efficient pinocytosis activity. Mature DC were CD14-/CD83+ and acted as potent stimulators of allogeneic naïve T-cells. When differentiation/maturation was performed in the presence of glioma-CM, a dose-dependent inhibition of CD14 down-regulation as well as of CD83 up-regulation after induction of DC maturation was observed. Pinocytosis-activity of immature DC was inhibited in the presence of U373-CM, whereas A172-CM had no suppressive effect on antigen-uptake activity. Consistent with down-regulation of adhesion (CD54), co-stimulatory (CD40, CD80, CD86) and HLA-class I and II molecules on mature DC and absent expression of IL-12 and of the chemokines MCP-1 - 4 in the presence of glioma conditioned medium, naïve T-cell proliferative and TH1-cytokine (IL-2, IFNγ) responses were reduced.

Conclusions: Malignant glioma cells secret factors, which interfere with DC differentiation/maturation and function. These factors probably are part of the immune escape strategies established in gliomas and, thus, may contribute to prevent induction of anti-glioma immune responses.