title: Adaptive Immune Response to and Survival Effect of Temozolomide- and Valproic Acid-induced Autophagy in Glioblastoma.
abstract: OBJECTIVE
  The combination of radiotherapy, temozolomide and valproic acid (VPA) has shown some promise in retrospective analyses of patients with glioblastoma, although their mechanisms of action remain unknown.
  
  
  METHODS
  We investigated the in vitro and in vivo effects of pretreating glioma cells with temozolomide and VPA as an immunization strategy to boost an adaptive immune response in a syngeneic mouse model.
  
  
  RESULTS
  Temozolomide and VPA induced autophagy in GL261 glioma cells, and caused tumor antigen-specific T-cells to become activated effector T-cells. Mice with a pre-existing glioma showed no improvement in clinical outcome when immunized with temozolomide- and VPA-treated glioma cells.
  
  
  CONCLUSIONS
  Although temozolomide and VPA treatment of glioma cells can boost the adaptive immune response, in the context of a vaccine therapy, additional factors are necessary to eradicate the tumor and improve survival.
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Proske
authors.affiliation: Department of Dermatology, University Hospital, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Walter
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bumes
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hutterer
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Arabel
authors.initials: A
authors.lastname: Vollmann-Zwerenz
authors.affiliation: Department of Neurosurgery, University Hospital, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Ilker Y
authors.initials: IY
authors.lastname: Eyüpoglu
authors.affiliation: Department of Neurosurgery, University Hospital, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Nicolai E
authors.initials: NE
authors.lastname: Savaskan
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Seliger
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.affiliation: Department of Neurology, University Hospital, University of Erlangen-Nürnberg, Erlangen, Germany martin.uhl@uk-erlangen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Uhl
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D051379:Mice; D012189:Retrospective Studies; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D019496:Cancer Vaccines; D014635:Valproic Acid; D003606:Dacarbazine; D000077204:Temozolomide
keywords: CD8 T-cells; Temozolomide; autophagy; dendritic cells; glioblastoma; valproic acid