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

Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types. 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-methylg...

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Veröffentlicht in:Neuro-oncology (Charlottesville, Va.) Va.), 2015-08, Vol.17 (8), p.1064-1075
Hauptverfasser: 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
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container_end_page 1075
container_issue 8
container_start_page 1064
container_title Neuro-oncology (Charlottesville, Va.)
container_volume 17
creator 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
description Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types. 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. 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. 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.
doi_str_mv 10.1093/neuonc/nou307
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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. 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 &lt; .001), CD8+ (P &lt; .001), CD20+ TIL density (P &lt; .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. TILs and PD-L1 expression are detectable in the majority of glioblastoma samples but are not related to outcome. 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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. 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 &lt; .001), CD8+ (P &lt; .001), CD20+ TIL density (P &lt; .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. 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.</abstract><cop>England</cop><pmid>25355681</pmid><doi>10.1093/neuonc/nou307</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Aged
Aged, 80 and over
B7-H1 Antigen - 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
title Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma
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