Adaptive Immune Response to and Survival Effect of Temozolomide- and Valproic Acid-induced Autophagy in Glioblastoma

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. We investigated the in vitro and in vivo effects of pretreating glioma cells with temozolomide and...

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Bibliographic Details
Published in:Anticancer research 2016-03, Vol.36 (3), p.899
Main Authors: Proske, Judith, Walter, Lisa, Bumes, Elisabeth, Hutterer, Markus, Vollmann-Zwerenz, Arabel, Eyüpoglu, Ilker Y, Savaskan, Nicolai E, Seliger, Corinna, Hau, Peter, Uhl, Martin
Format: Article
Language:English
Subjects:
Adaptive Immunity - drug effects
Animals
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Autophagy - drug effects
Brain Neoplasms - drug therapy
Brain Neoplasms - immunology
Brain Neoplasms - mortality
Cancer Vaccines - administration & dosage
Cancer Vaccines - pharmacology
Cell Line, Tumor
Dacarbazine - administration & dosage
Dacarbazine - analogs & derivatives
Dacarbazine - pharmacology
Glioblastoma - drug therapy
Glioblastoma - immunology
Glioblastoma - mortality
Mice
Retrospective Studies
Survival Analysis
Treatment Outcome
Valproic Acid - administration & dosage
Valproic Acid - pharmacology
Xenograft Model Antitumor Assays
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Summary: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. 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. 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. 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.
ISSN:1791-7530