Comprehensive analysis of PD-L1 expression in glioblastoma multiforme.
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.
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Dieter Henrik
DH
Heiland
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Gerrit
G
Haaker
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Daniel
D
Delev
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Bianca
B
Mercas
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Waseem
W
Masalha
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Sabrina
S
Heynckes
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Annette
A
Gäbelein
Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Dietmar
D
Pfeifer
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Maria Stella
MS
Carro
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Astrid
A
Weyerbrock
Institute of Neuropathology, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, Germany.
Marco
M
Prinz
Department of Neurosurgery, Medical Center - University of Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Germany.
Oliver
O
Schnell
D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D056747:Immunomodulation; D009154:Mutation; D060787:Neoplasm Grading; D020543:Proteome; D040901:Proteomics / Q000379:methods
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D020543:Proteome
PD-L1; WGCNA; glioblastoma multiforme; immunotherapy; integrative analysis