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59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

01. - 04.06.2008, Würzburg

Immunomodulating activity of 5-ALA based photodynamic therapy of human gliomas

Immunmodulierende Wirkung der 5-ALA basierten photodynamischen Therapie von humanen Glioblastomen

Meeting Abstract

  • corresponding author N. Etminan - Neurochirurgische Klinik, Klinikum der Heinrich-Heine Universität, Düsseldorf
  • R. V. Sorg - Institut für Transplantationsdiagnostik und Zelltherapeutika, Klinikum der Heinrich-Heine Universität, Düsseldorf
  • J. Ficnar - Neurochirurgische Klinik, Klinikum der Heinrich-Heine Universität, Düsseldorf
  • H.-J. Steiger - Neurochirurgische Klinik, Klinikum der Heinrich-Heine Universität, Düsseldorf
  • W. Stummer - Neurochirurgische Klinik, Klinikum der Heinrich-Heine Universität, Düsseldorf

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP 077

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc345.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Etminan 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: 5-ALA-based photodynamic therapy (PDT) can improve clinical outcome in patients suffering from recurrent glioblastoma and causes long-sustaining responses. Due to the limited penetration (Δeff=3mm) of the laser light in the brain tissue, however, additional mechanisms have to be involved in the elimination of more distant infiltrating tumor cells. To determine whether an immunological component plays a role, the impact of ALA/PDT on the afferent phase of adaptive immunity was studied.

Methods: Human glioma spheroids (U373, A172 cells) were treated with ALA/PDT, labelled with the fluorescent dye CFSE and co-cultured with immature dendritic cells (DC) to determine uptake of tumor material by the DC. To study maturation of DC, immature DC were co-cultured with spheroid-conditioned medium, and maturation was monitored by flow-cytometry.

Results: Immature dendritic cells co-cultured with tumor spheroids revealed uptake of tumor material, which was localized perinuclearly in the DC. Flow cytometric evaluation demonstrated a significantly enhanced uptake of material derived from ALA/PDT treated spheroids compared to control spheroids (16.8±5.3% vs. 1.9±.0.8% CFSE+ DC; p≤0,05). At the same time, spheroids caused maturation of DC, as indicated by up-regulation of the mature DC-associated surface molecule CD83. The mean CD83 expression of DC matured in the presence of spheroid-conditioned medium was 42.9±8.7% (p≤0,001) compared to 2.9±2.2% in control cultures. Thus, spheroids induced a similar level of maturation as the potent maturation stimulus TNFα (55.2±21.8% CD83+ DC).

Conclusions: ALA/PDT treatment of glioma-spheroids promotes the two initial steps of the afferent phase of adaptive immunity. This suggests that ALA/PDT therapy may contribute to the induction of anti-tumoral immune responses in glioma patients.