gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

Dendritic cell activation by aminolevulinic acid-mediated photodynamic treatment of human glioblastoma spheroids

Meeting Abstract

  • N. Etminan - Neurochirurgische Klinik, Heinrich-Heine Universität, Düsseldorf
  • C. Peters - Neurochirurgische Klinik, Heinrich-Heine Universität, Düsseldorf; Institut für Transplantations Diagnostik and Zell Therapeutika, Heinrich-Heine Universität, Düsseldorf
  • H.J. Steiger - Neurochirurgische Klinik, Heinrich-Heine Universität, Düsseldorf
  • R.V. Sorg - Institut für Transplantations Diagnostik and Zell Therapeutika, Heinrich-Heine Universität, Düsseldorf

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMO.05.07

DOI: 10.3205/11dgnc026, URN: urn:nbn:de:0183-11dgnc0260

Published: April 28, 2011

© 2011 Etminan et al.
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Outline

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Objective: Aminolevulinic acid-mediated photodynamic therapy (ALA/PDT) in glioblastoma patients allows for induction of long-sustaining clinical responses and can improve survival of patients, suggesting an immunological component to PDT even for cranial tumors. For such immunological responses to occur, immature dendritic cells (DC) have to migrate to the tumor, take up tumor antigens and respond to local danger signals with maturation, before they engage in T-cell activation. Therefore, we have studied the effect of 5-aminolevulinic acid (ALA)-mediated PDT on DC in a human spheroid model of glioblastoma multiforme.

Methods: ALA/PDT-treated spheroids of the glioma cell lines U87 and U251 were studied in a Boyden-chamber assay for their chemo-attractive activity for immature DC. Untreated spheroids or spheroids that had been treated with either irradiation or ALA alone served as controls. Uptake of tumor antigens from the spheroids was determined after co-culture of immature DC with fluorescently labelled spheroids by flow cytometry. Induction of DC maturation by the spheroids was evaluated by determining expression of DC maturation markers by flow cytometry and of the allostimulatory potential of the DC.

Results: ALA/PDT-treated glioma spheroids were attractants for immature DC, which migrated towards the spheroids with a significantly increased rate as compared to control targets. When co-cultured with the ALA/PDT-treated spheroids, immature DC acquired tumor antigens effectively in a heat shock protein 70-dependent manner, which they did not from control spheroids. Moreover, co-culture with ALA/PDT-treated spheroids induced DC maturation as indicated by the up-regulation of CD83, CD80 and CD86 as well as increased T-cell stimulatory activity of the DC.

Conclusions: ALA/PDT treatment of glioma spheroids promotes the three initial steps of the afferent phase of adaptive immunity, attraction, antigen uptake and maturation of DC, a prerequisite for the induction of anti-tumoral T-cell responses in GBM