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

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State: Public
Version: Final published version
Serval ID
serval:BIB_DEB614299DDB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma.
Journal
Neuro-oncology
Author(s)
Berghoff A.S., Kiesel B., Widhalm G., Rajky O., Ricken G., Wöhrer A., Dieckmann K., Filipits M., Brandstetter A., Weller M., Kurscheid S., Hegi M.E., Zielinski C.C., Marosi C., Hainfellner J.A., Preusser M., Wick W.
ISSN
1523-5866 (Electronic)
ISSN-L
1522-8517
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
17
Number
8
Pages
1064-1075
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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
Adult, Aged, Aged, 80 and over, Antigens, CD274/metabolism, Brain Neoplasms/metabolism, Brain Neoplasms/mortality, Glioblastoma/metabolism, Glioblastoma/mortality, Humans, Kaplan-Meier Estimate, Lymphocytes, Tumor-Infiltrating/metabolism, Middle Aged, PTEN Phosphohydrolase/metabolism, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
13/10/2015 19:13
Last modification date
20/08/2019 17:03
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