gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

5-ALA based Photodynamic Therapy (PDT) of human glioma spheroids stimulates the afferent phase of cellular immunity

Meeting Abstract

  • N. Etminan - Neurochirurgische Klinik, Universitätsklinikum Düsseldorf
  • R. Sorg - Institut für Transplantationsdiagnostik und Zelltherapeutika, Universitätsklinikum Düsseldorf
  • D. Lakbir - Institut für Transplantationsdiagnostik und Zelltherapeutika, Universitätsklinikum Düsseldorf
  • S. Anlasik - Neurochirurgische Klinik, Universitätsklinikum Düsseldorf
  • H.-J. Steiger - Neurochirurgische Klinik, Universitätsklinikum Düsseldorf
  • W. Stummer - Neurochirurgische Klinik, Universitätsklinikum Düsseldorf

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP06-07

DOI: 10.3205/09dgnc311, URN: urn:nbn:de:0183-09dgnc3115

Published: May 20, 2009

© 2009 Etminan et al.
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Outline

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Objective: Long ranging responses after ALA/PDT of glioma patients suggest additional mechanisms of tumor control apart from the limited photochemical destruction of the tumor. To determine whether ALA/PDT causes local stimulation of anti-tumoral immunity, we have studied the effects of PDT on dendritic cell (DC) function, and thus on the afferent phase of an anti-tumoral immune response.

Methods: ALA/PDT treated glioma spheroids (U373, U87, U251) were used to study effects on chemoattraction (Boyden chamber assay) as well as antigen-uptake activity (flow cytometry) of immature DC. Modulation of DC maturation status was assessed by determining expression of co-stimulatory and HLA-molecules on DC by flow cytometry after co-culture with the spheroids. Untreated spheroids or spheroids which had been treated with ALA or irradiation alone served as controls.

Results: ALA/PDT treated glioma spheroids revealed a distinct chemoattractive effect on immature DC, which migrated towards the spheroids with an increased rate (2.3±0.4-fold, p<0.001) as compared to controls. Confrontation of immature DC with tumor spheroids significantly increased antigen-uptake activity by DCs, (1.8±0.1-fold) which also resulted in a substantial uptake of tumor antigens by spheroids. Tumor antigen uptake from ALA/PDT treated and untreated tumor spheroids by DC measured 74.7±9.1% vs. 7.3±1.5% respectively. Moreover, co-cultivation with ALA/PDT treated spheroids induced DC maturation as evidenced by significant up-regulation of CD83, CD80 and CD86 antigens. In the presence of ALA/PDT treated spheroids, 31.3±4.7% of DC acquired the mature DC marker CD83 as compared to 4.3±2.4% in control cultures.

Conclusions: ALA/PDT treatment of glioma spheroids significantly promotes the three initial steps of the afferent phase of cellular adaptive immunity: chemoattraction of immature DC, enhanced antigen uptake and induction of DC maturation. Thus, ALA/PDT apparently generates a local immunostimulatory environment which may result in an induction of anti-tumoral immunity.