Artikel
The immunogenic effect of 5-ALA-Photodynamic Therapy
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Autoren
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Nima Etminan
- Klinik für Neurochirurgie, Heinrich-Heine-Universität, Düsseldorf, Germany
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Corinna Peters
- Klinik für Neurochirurgie, Institut für Transplantationsdiagnostik and Zelltherapeutika, Heinrich-Heine-Universität, Düsseldorf, Germany
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Walter Stummer
- Klinik für Neurochirurgie, Klinik für Neurochirurgie, Universitätsklinikum Münster, Germany
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Hans-Jakob Steiger
- Klinik für Neurochirurgie, Heinrich-Heine-Universität, Düsseldorf, Germany
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Rüdiger Volker Sorg
- Institut für Transplantationsdiagnostik and Zelltherapeutika, Heinrich-Heine-Universität, Düsseldorf, Germany
| Veröffentlicht: | 16. September 2010 |
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Gliederung
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Objective: 5-Aminolevulinic acid-mediated photodynamic therapy (ALA/PDT) can improve clinical outcome in patients suffering from glioblastoma multiforme (GBM). Due to the limited penetration of the laser light into brain tissue, however, additional mechanisms besides direct phototoxicity have to be involved in eliminating the more distant infiltrating tumor cells. Therefore the effect of ALA/PDT on the afferent phase of adaptive antitumoral-immunity was studied.
Methods: Human glioblastoma spheroids (U251, U87) were treated with ALA/PDT and the effect on the activity of human Dendritic cells (DC) was studied. Chemoattraction was studied using the Boyden-Chamber migration assay. Tumor material uptake was evaluated by flow cytometry, after CFSE-fluorescent labeling of tumor cells. The impact of ALA/PDT treated spheroids on DC maturation and function was studied in Co-cultures and quantified flowcytometrically and by determining the allo-stimulatory activity of the DC.
Results: ALA/PDT-treated glioma spheroids attract immature dendritic cells, whereas control spheroids did not display significant chemoattraction. The resulting vicinity of ALA/PDT-treated spheroids and DC allows effective uptake of tumor antigens. Even when control spheroids are cocultivated with DC, no significant uptake of tumor material was evident.
Moreover, ALA/PDT appears to generate immuno-stimulatory signals inducing DC maturation. CD83, CD80 and CD86 are significantly upregulated and an ALA/PDT-specific enhancement of T-cell stimulatory activity was observed.
Conclusions: ALA/PDT treatment of glioma spheroids stimulates the afferent phase of adaptive antitumoral-immunity, which may contribute to the beneficial effect of ALA/PDT treatment in patients with glioblastoma.
