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

Abstract

// Sabrina Heynckes 1, 5 , Annette Gaebelein 1, 5 , Gerrit Haaker 1, 5 , Jürgen Grauvogel 1, 5 , Pamela Franco 1, 5 , Irina Mader 2, 5 , Maria Stella Carro 1, 5 , Marco Prinz 3, 4, 5 , Daniel Delev 1, 5 , Oliver Schnell 1, 5, * and Dieter Henrik Heiland 1, 5, * 1 Department of Neurosurgery, Medical Center, University of Freiburg, Freiburg, Germany 2 Department of Neuroradiology, Medical Center, University of Freiburg, Freiburg, Germany 3 BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany 4 Institute of Neuropathology, Medical Center, University of Freiburg, Freiburg, Germany 5 Faculty of Medicine, University of Freiburg, Freiburg, Germany * These authors have contributed equally to this work Correspondence to: Dieter Henrik Heiland, email: dieter.henrik.heiland@uniklinik-freiburg.de 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 .