Oncotarget

Research Papers:

Comprehensive analysis of PD-L1 expression in glioblastoma multiforme

Dieter Henrik Heiland _, Gerrit Haaker, Daniel Delev, Bianca Mercas, Waseem Masalha, Sabrina Heynckes, Annette Gabelein, Dietmar Pfeifer, Maria Stella Carro, Astrid Weyerbrock, Marco Prinz & Oliver Schnell

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Oncotarget. 2017; 8:42214-42225. https://doi.org/10.18632/oncotarget.15031

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Abstract

Dieter Henrik Heiland1,4, Gerrit Haaker1,4, Daniel Delev1,4, Bianca Mercas1,4, Waseem Masalha1,4, Sabrina Heynckes1,4, Annette Gäbelein1,4, Dietmar Pfeifer2,4, Maria Stella Carro1,4, Astrid Weyerbrock1,4, Marco Prinz3,4,5 and Oliver Schnell1,4

1Department of Neurosurgery, Medical Center - University of Freiburg, Baden-Württemberg, Germany

2Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Baden-Württemberg, Germany

3Institute of Neuropathology, Medical Center - University of Freiburg, Baden-Württemberg, Germany

4Faculty of Medicine, University of Freiburg, Baden-Württemberg, Germany

5BIOSS Centre for Biological Signalling Studies, University of Freiburg, Baden-Württemberg, Germany

Correspondence to:

Dieter Henrik Heiland, email: dieter.henrik.heiland@uniklinik-freiburg.de

Keywords: glioblastoma multiforme, PD-L1, WGCNA, integrative analysis, immunotherapy

Received: September 09, 2016     Accepted: January 10, 2017     Published: February 02, 2017

ABSTRACT

Glioblastoma multiforme are highly malignant brain tumours with frequent genetic and epigenetic alterations. The poor clinical outcome of these tumours necessitates the development of new treatment options. Immunotherapies for glioblastoma multiforme including PD1/PD-L1 inhibition are currently tested in ongoing clinical trials. The purpose of this study was to investigate the molecular background of PD-L1 expression in glioblastoma multiforme and to find associated pathway activation and genetic alterations. We show that PD-L1 is up-regulated in IDH1/2 wildtype glioblastoma multiforme compared to lower-grade gliomas. In addition, a strong association of PD-L1 with the mesenchymal expression subgroup was observed. Consistent with that, NF1 mutation and corresponding activation of the MAPK pathway was strongly connected to PD-L1 expression. Our findings may explain different response to PD-L1 inhibition of patients in ongoing trials and may help to select patients that may profit of immunotherapy in the future.


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