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Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma

Berghoff, Anna Sophie ; Kiesel, Barbara ; Widhalm, Georg ; Rajky, Orsolya ; Ricken, Gerda ; Wöhrer, Adelheid ; Dieckmann, Karin ; Filipits, Martin ; Brandstetter, Anita ; Weller, Michael ; Kurscheid, Sebastian ; Hegi, Monika E. ; Zielinski, Christoph C. ; Marosi, Christine ; Hainfellner, Johannes A. ; Preusser, Matthias ; Wick, Wolfgang

In: Neuro-Oncology, 2015, vol. 17, no. 8, p. 1064-1075

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    Titre
    • Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma
    Auteur
    • Berghoff, Anna Sophie. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Kiesel, Barbara. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Widhalm, Georg. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Rajky, Orsolya. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Ricken, Gerda. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Wöhrer, Adelheid. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Dieckmann, Karin. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Filipits, Martin. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Brandstetter, Anita. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Weller, Michael. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Kurscheid, Sebastian. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Hegi, Monika E.. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Zielinski, Christoph C.. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Marosi, Christine. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Hainfellner, Johannes A.. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Preusser, Matthias. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    • Wick, Wolfgang. Institute of Neurology, Medical University of Vienna, Vienna, Department of Medicine I, Vienna, Comprehensive Cancer Center, Vienna, Department of Neurosurgery, Department of Radiotherapy, Vienna, Department of Neurology, Zurich, Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, Lausanne, Neurology Clinic and National Center for Tumor Disease, Heidelberg, Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Austria, Austria, Austria, Austria, Austria, Switzerland, Switzerland, Germany, Germany
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Neuro-Oncology, 2015, vol. 17, no. 8, p. 1064-1075. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:303983
    Summary
    Background Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types. Methods We performed immunohistochemistry for CD3, CD8, CD20, HLA-DR, phosphatase and tensin homolog (PTEN), PD-1, and PD-L1 and pyrosequencing for assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status in 135 glioblastoma specimens (117 initial resection, 18 first local recurrence). PD-L1 gene expression was analyzed in 446 cases from The Cancer Genome Atlas. Results Diffuse/fibrillary PD-L1 expression of variable extent, with or without interspersed epithelioid tumor cells with membranous PD-L1 expression, was observed in 103 of 117 (88.0%) newly diagnosed and 13 of 18 (72.2%) recurrent glioblastoma specimens. Sparse-to-moderate density of tumor-infiltrating lymphocytes (TILs) was found in 85 of 117 (72.6%) specimens (CD3+ 78/117, 66.7%; CD8+ 52/117, 44.4%; CD20+ 27/117, 23.1%; PD1+ 34/117, 29.1%). PD1+ TIL density correlated positively with CD3+ (P < .001), CD8+ (P < .001), CD20+ TIL density (P < .001), and PTEN expression (P = .035). Enrichment of specimens with low PD-L1 gene expression levels was observed in the proneural and G-CIMP glioblastoma subtypes and in specimens with high PD-L1 gene expression in the mesenchymal subtype (P = 5.966e-10). No significant differences in PD-L1 expression or TIL density between initial and recurrent glioblastoma specimens or correlation of PD-L1 expression or TIL density with patient age or outcome were evident. Conclusion TILs and PD-L1 expression are detectable in the majority of glioblastoma samples but are not related to outcome. Because the target is present, a clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastoma