gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Immune escape in glioblastoma: Interference with dendritic cell differentiation and maturation

Immune Escape-Mechanismen bei malignen Gliomen: Interferenz mit der Differenzierung und Ausreifung dendritischer Zellen

Meeting Abstract

Suche in Medline nach

  • corresponding author Michael Christoph Sabel - Department of Neurosurgery, Heinrich-Heine-University Medical Center, Düsseldorf
  • Z. Özcan - Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Medical Center, Düsseldorf
  • M. Gorol - Department of Neurosurgery, Heinrich-Heine-University Medical Center, Düsseldorf
  • R. V. Sorg - Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Medical Center, Düsseldorf

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocMO.04.02

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0045.shtml

Veröffentlicht: 23. April 2004

© 2004 Sabel et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Dendritic cells (DC) are specialized antigen presenting cells, critical to initiation of T-cell responses. Therefore, they are pivotal to anti-tumour immunity. Tumour cells, however, due to permanent immune surveillance, have developed multiple strategies, to evade the immune system, including mechanisms, which interfere with DC function. To identify such immune escape mechanisms in malignant gliomas, interference of the cell lines U373 and A172 with DC differentiation and maturation was studied.

Methods

Monocytes were enriched immunomagnetically to 98.0 ± 0.2% CD14+ purity and cultured under serum-free conditions in the presence of GM-CSF and IL-4 for 6 days, to induced immature DC generation, followed by an additional 3-day culture period in the presence of GM-CSF, IL-4 and TNFα, to induce DC maturation. The effect of glioma cells was determined by addition of conditioned medium (CM) at the onset of cultures (n≥3).

Results

Immature DC showed mainly a CD14- (5.3±2.0%) CD83- (8.4±5.3%) phenotype and revealed potent pinocytosis activity. Presence of U373-CM and A172-CM inhibited down-regulation of the monocyte marker CD14, resulting in 40.8±14.5% and 42.0±3.3% residual CD14+ cells, respectively. Pinocytosis activity of the immature DC was inhibited by 82,0% and 31,6%, respectively. After 9 days of culture, DC had up-regulated the mature DC marker CD83 but lost CD14. In the presence of U373-CM and A172-CM, up-regulation of CD83 was inhibited by 90.1±2.0% and 67.9±19.6%, respectively. Interestingly, this inhibition of DC maturation was not associated with differences in adhesion and co-stimulatory expression. In an initial attempt to identify candidate molecules of immune interference in U373- and A172-CM, Luminex cytokine analysis and cytokine protein array analysis were performed, showing expression of e.g. IL-6, VEGF and TGFβ2, all of which may play a role.

Conclusions

Glioblastoma cells secrete factors, which inhibit DC differentiation and maturation.