Oncotarget

Research Papers:

Expression differences of programmed death ligand 1 in de-novo and recurrent glioblastoma multiforme

Sabrina Heynckes, Annette Gaebelein, Gerrit Haaker, Jürgen Grauvogel, Pamela Franco, Irina Mader, Maria Stella Carro, Marco Prinz, Daniel Delev, Oliver Schnell and Dieter Henrik Heiland _

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Oncotarget. 2017; 8:74170-74177. https://doi.org/10.18632/oncotarget.18819

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Abstract

Sabrina Heynckes1,5, Annette Gaebelein1,5, Gerrit Haaker1,5, Jürgen Grauvogel1,5, Pamela Franco1,5, Irina Mader2,5, Maria Stella Carro1,5, Marco Prinz3,4,5, Daniel Delev1,5, Oliver Schnell1,5,* and Dieter Henrik Heiland1,5,*

1Department of Neurosurgery, Medical Center, University of Freiburg, Freiburg, Germany

2Department of Neuroradiology, Medical Center, University of Freiburg, Freiburg, Germany

3BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany

4Institute of Neuropathology, Medical Center, University of Freiburg, Freiburg, Germany

5Faculty of Medicine, University of Freiburg, Freiburg, Germany

*These authors have contributed equally to this work

Correspondence to:

Dieter Henrik Heiland, email: [email protected]

Keywords: immune checkpoints, PD-L1, GBM, recurrent GBM

Received: May 13, 2017    Accepted: May 23, 2017    Published: June 28, 2017

ABSTRACT

The biology of recurrent glioblastoma multiforme (GBM) is a dynamic process influenced by selection pressure induced by different antitumoural therapies. The poor clinical outcome of tumours in the recurrent stage necessitates the development of effective therapeutic strategies. Checkpoint-inhibition (PD1/PD-L1 Inhibition) is a hallmark of immunotherapy being investigated in ongoing clinical trials. The purpose of this study was to analyse the PD-L1 expression in de-novo and recurrent glioblastoma multiforme and to explore associated genetic alterations and clinical traits. We show that PD-L1 expression was reduced in recurrent GBM in comparison to de-novo GBM. Additionally, patients who received an extended dose of temozolomide (TMZ) chemotherapy showed a significantly reduced level of PD-L1 expression in the recurrence stage compared to the corresponding de-novo tumour. Our findings may provide an explanation for potentially lower response to immunotherapy in the recurrent stage due to the reduced expression of the therapeutic target PD-L1.


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