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Comprehensive analysis of PD-L1 expression in glioblastoma multiforme

2017; Impact Journals LLC; Volume: 8; Issue: 26 Linguagem: Inglês

10.18632/oncotarget.15031

1949-2553

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

Ferroptosis and cancer prognosis

// Dieter Henrik Heiland 1, 4 , Gerrit Haaker 1, 4 , Daniel Delev 1, 4 , Bianca Mercas 1, 4 , Waseem Masalha 1, 4 , Sabrina Heynckes 1, 4 , Annette Gäbelein 1, 4 , Dietmar Pfeifer 2, 4 , Maria Stella Carro 1, 4 , Astrid Weyerbrock 1, 4 , Marco Prinz 3, 4, 5 and Oliver Schnell 1, 4 1 Department of Neurosurgery, Medical Center - University of Freiburg, Baden-Württemberg, Germany 2 Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Baden-Württemberg, Germany 3 Institute of Neuropathology, Medical Center - University of Freiburg, Baden-Württemberg, Germany 4 Faculty of Medicine, University of Freiburg, Baden-Württemberg, Germany 5 BIOSS 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.