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Neuro Oncol. 2015 Aug;17(8):1064-75. doi: 10.1093/neuonc/nou307. Epub 2014 Oct 29.

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

Author information

1
Institute of Neurology, Medical University of Vienna, Vienna, Austria (A.S.B., G.R., A.W., J.A.H.); Department of Medicine I, Medical University of Vienna, Vienna, Austria (A.S.B., O.R., M.F., A.B., C.C.Z., C.M., M.P.); Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria (A.S.B., B.K., G.W., O.R., G.R., A.W., K.D., M.F., A.B., C.C.Z., C.M., J.A.H., M.P.); Department of Neurosurgery, Medical University of Vienna, Vienna, Austria (B.K., G.W.); Department of Radiotherapy, Medical University of Vienna, Vienna, Austria (K.D.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (M.W.); Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery, Department of Clinical Neurosciences, University Hospital Lausanne (CHUV), Lausanne, Switzerland (S.K., M.E.H.); Neurology Clinic and National Center for Tumor Disease, University of Heidelberg, Heidelberg, Germany (W.W.); Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany (W.W.).

Abstract

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.

KEYWORDS:

glioblastoma; immune checkpoint; programmed death 1; programmed death ligand 1

PMID:
25355681
PMCID:
PMC4490866
DOI:
10.1093/neuonc/nou307
[Indexed for MEDLINE]
Free PMC Article

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