Article
5-ALA based Photodynamic Therapy (PDT) of human glioma spheroids stimulates the afferent phase of cellular immunity
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Published: | May 20, 2009 |
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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.