title: Heat-shock protein 70-dependent dendritic cell activation by 5-aminolevulinic acid-mediated photodynamic treatment of human glioblastoma spheroids in vitro.
abstract: BACKGROUND
  T-cell responses contribute to the anti-tumoural effect of photodynamic therapy (PDT). For such responses to occur, dendritic cells (DCs) have to migrate to the tumour, take up tumour antigens and respond to danger signals with maturation, before they engage in T-cell activation. Here, we have studied the effect of 5-aminolevulinic acid (ALA)-mediated PDT on DCs in vitro in a human spheroid model of glioblastoma (GB).
  
  
  METHODS
  Spheroids of the GB cell lines U87 and U251 were treated with ALA/PDT, and effects on attraction, uptake of tumour antigens and maturation of DCs were studied. To block heat-shock protein-70 (HSP-70) on the spheroids, neutralising antibodies were used.
  
  
  RESULTS
  5-Aminolevulinic acid /PDT-treated GB spheroids attracted DCs that acquired tumour antigens from the spheroids effectively. Moreover, co-culture with ALA/PDT-treated spheroids induced DC maturation as indicated by the upregulation of CD83 and co-stimulatory molecules as well as increased T-cell stimulatory activity of the DCs. Heat-shock protein-70 was upregulated on the spheroids after ALA/PDT treatment. Uptake of tumour antigens and DC maturation induced by the ALA/PDT-treated spheroids were inhibited when HSP-70 was blocked.
  
  
  CONCLUSIONS
  ALA/PDT treatment of glioma spheroids promotes the three initial steps of the afferent phase of adaptive immunity, which is at least partially mediated by HSP-70.
authors.affiliation: Department of Neurosurgery, Heinrich-Heine-University Hospital, Bldg. 13.71, Moorenstrasse 5, Düsseldorf 40225, Germany. etminan@uni-duesseldorf.de
authors.forename: N
authors.initials: N
authors.lastname: Etminan
authors.forename: C
authors.initials: C
authors.lastname: Peters
authors.forename: D
authors.initials: D
authors.lastname: Lakbir
authors.forename: E
authors.initials: E
authors.lastname: Bünemann
authors.forename: V
authors.initials: V
authors.lastname: Börger
authors.forename: M C
authors.initials: MC
authors.lastname: Sabel
authors.forename: D
authors.initials: D
authors.lastname: Hänggi
authors.forename: H-J
authors.initials: HJ
authors.lastname: Steiger
authors.forename: W
authors.initials: W
authors.lastname: Stummer
authors.forename: R V
authors.initials: RV
authors.lastname: Sorg
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D018874:Spheroids, Cellular / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D018840:HSP70 Heat-Shock Proteins; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid