gms | German Medical Science

68th Annual Meeting of the German Society of Neurosurgery (DGNC)
7th Joint Meeting with the British Neurosurgical Society (SBNS)

German Society of Neurosurgery (DGNC)

14 - 17 May 2017, Magdeburg

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Comprehensive analysis of immunology in recurrent glioblastoma multiforme

Meeting Abstract

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  • Dieter Henrik Heiland - Department of Neurosurgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Deutschland
  • Sabrina Heynckes - Department of Neurosurgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Deutschland
  • Annette Gäbelein - Department of Neurosurgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Deutschland
  • Gerrit Haaker - Department of Neurosurgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Deutschland
  • Pamela Franco Jimenez - Department of Neurosurgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Deutschland
  • Irina Mader - Klinik für Neuroradiologie, Klinik für Neuroradiologie, Bad Krozingen, Deutschland
  • Dietmar Pfeifer - Universitätsklinikum Freiburg, Klinik für Hämatologie, Onkologie und Stammzelltransplantation, Freiburg, Deutschland
  • Marco Prinz - Universitätsklinikum Freiburg, Institut für Neuropathologie, Freiburg, Deutschland
  • Daniel Delev - Department of Neurosurgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Deutschland
  • Oliver Schnell - Department of Neurosurgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. Society of British Neurological Surgeons. 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS). Magdeburg, 14.-17.05.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocMi.28.02

doi: 10.3205/17dgnc559, urn:nbn:de:0183-17dgnc5599

Published: June 9, 2017

© 2017 Heiland et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

Text

Objective: The biology of recurrent glioblastoma is a dynamic process influenced by selection pressure induced by different antitumoral therapies. The characteristics of these biological processes have been rarely explored, which complicates treatment. Checkpoint-inhibition (PD1/PD-L1 Inhibition) is a hallmark of immunotherapy, which is being investigated for recurrent GBM in ongoing clinical trials. The purpose of this study was to analyse the PD-L1 expression in de-novo/recurrent glioblastoma multiforme and to explore associated genetic alterations.

Methods: 105 tissue samples of 56 glioblastoma patients were acquired by neuronavigation-guided resection between 2011 and 2014 in the Department of Neurosurgery, Medical Center University of Freiburg. Comprehensive transcriptional network analysis was performed by expression array data of 49 patients and validated by available data sets (TCGA and Bai et al.). Quantification of the PD-L1 level was performed by immunohistochemistry, immunofluorescence, western blot and qRT-PCR.

Results: Comprehensive transcriptional network analysis showed a strong connection between MAPK pathway activation and increased level of PD-L1. Additionally, PD-L1 expression was found to be associated with mesenchymal gene expression and immune response pathway up-regulation. However, the immune related pathways were down-regulated in recurrent glioblastoma. Recurrent GBM showed decreased mRNA expression-levels of PD-L1 in comparison to de-novo tumors. These findings were validated by additional immunostainings and western blot analysis. A multivariate regression model showed a significantly lower PD-L1-expression in recurrent glioblastoma associated with an extended temozolomide treatment.

Conclusion: We showed that PD-L1 expression and immune related pathway activation are reduced in recurrent GBM in comparison to de-novo GBM. Additionally, patients who received an extended dose of temozolomide chemotherapy showed a significantly lower level of PD-L1 expression in the recurred tumour stage. Our findings may therefore provide an explanation for reduced effectiveness of immunotherapy in recurrent GBM.