{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:39:09Z","timestamp":1790404749247,"version":"4.1.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurosurg.","NEUROS"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Checkpoint inhibition has demonstrated clinical efficacy in a variety of solid tumors. Reports of programmed death ligand 1 (PD-L1) expression in glioblastoma are highly variable (ranging from 6% to 88%) and its role as a prognostic marker has yielded conflicting results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>To validate the prevalence and prognostic role of PD-L1 expression in a large cohort of diffuse gliomas according to the 2016 revised WHO classification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Using tissue microarrays, we compared 5 PD-L1 monoclonal antibodies (n\u00a0=\u00a056) and validated expression (n\u00a0=\u00a0183) using quantitative immunohistochemistry (IHC) and RNA in situ hybridization (RISH). Expression data from The Cancer Genome Atlas (TCGA) and published studies were compared with clinical outcome. Multiplexed immunophenotyping was used to identify PD-L1+\u00a0cell populations in post-treatment glioblastoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Using a 5% cut-off, PD-L1 expression was significantly associated with a poor prognosis in both histologically defined (n\u00a0=\u00a0125, log-rank\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a0.001) and recurrent isocitrate dehydrogenase (IDH)-wildtype glioblastoma (n\u00a0=\u00a060, log-rank\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a0.015). PD-L1 remained a significant negative prognosticator in Cox regression analysis (hazard ratio: 1.96,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a0.021). Analysis of TCGA data confirmed decreased overall survival in recurrent non\u2013glioma CpG island methylator phenotype (G-CIMP) glioblastoma (n\u00a0=\u00a012, log-rank\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a0.023), but not in glioblastoma as a group (n\u00a0=\u00a0444, log-rank\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a0.135). PD-L1 RISH showed a significant correlation with IHC (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a0.0001). PD-L1 was observed in the proliferating perivascular stem cell and immune niche of post-treatment glioblastoma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>A 5% PD-L1 expression cut-off identified a subset of glioblastoma that is associated with a worse clinical outcome. This association remained significant within the newly defined IDH-wildtype classification. These findings could have implications for patient stratification in future clinical trials of PD-1\/PD-L1 blockade.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuros\/nyy268","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T15:10:44Z","timestamp":1526915444000},"page":"280-289","source":"Crossref","is-referenced-by-count":31,"title":["Programmed Death Ligand 1 Is a Negative Prognostic Marker in Recurrent Isocitrate Dehydrogenase-Wildtype Glioblastoma"],"prefix":"10.1227","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3583-8308","authenticated-orcid":false,"given":"Drew","family":"Pratt","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, Michigan"},{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, 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