Plasma PD-L1 as a biomarker in the clinical management of glioblastoma multiforme-a retrospective cohort study
Glioblastoma multiforme (GBM) is the most aggressive, malignant, and therapy-resistant tumor of the brain. Blockade therapy targeting the programmed cell death protein 1 (PD-1)/programmed death ligand (PD-L1) axis is currently under investigation for the clinical management of the GBM. This study ha...
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Published in | Frontiers in immunology Vol. 14; p. 1202098 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
17.07.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Glioblastoma multiforme (GBM) is the most aggressive, malignant, and therapy-resistant tumor of the brain. Blockade therapy targeting the programmed cell death protein 1 (PD-1)/programmed death ligand (PD-L1) axis is currently under investigation for the clinical management of the GBM. This study has quantified the plasma levels of PD-L1 as a biomarker for the clinical management of GBM.
A cohort (
= 128) of Pakistani adult glioblastoma patients together with age- and sex-matched healthy controls was used for quantification of pre-surgery levels of plasma PD-L1. PD-L1 protein and mRNA were measured by PD-L1 platinum enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. Receiver operating characteristic (ROC) curve analysis was used to compute area under the curve (AUC) for specificity and sensitivity analyses. The Kaplan-Meier survival analysis was employed to compute overall survival.
PD-L1 protein and mRNA were significantly higher in GBM compared to the healthy controls (
< 0.0001). Mean PD-L1 concentration for the GBM was found to be 48.98 ± 2.290 pg/ml compared to 27.63 ± 1.281 pg/ml for controls. Gene expression analysis showed statistically significant upregulation (
< 0.0001) of PD-L1 in blood of GBM compared to healthy controls. Plasma PD-L1 showed an AUC of 0.840 (
< 0.0001; 95% CI = 0.7716 to 0.9090) where a cutoff value higher than 46 pg/ml demonstrated 100% specificity and 57.81% sensitivity. Higher pre-surgery levels of PD-L1 were found to be associated with overall poor survival [
< 0.0001; HR (log-rank) = 0.08; 95% CI = 0.04 to 0.15]. Age, gender, and ethnic background were not found to be associated with plasma PD-L1 levels.
The study concludes that blood-based measurements of PD-L1 in GBM can be a promising prognostic marker and therapeutic target besides a rapid and relatively non-invasive screening tool for routine clinical management. Future work extending the analysis to larger cohorts through multi-center collaborations involving pre-treatment and post-treatment groups is required to fully explore the usefulness of circulating PD-L1 for effective clinical applications. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Michael C. Burger, Goethe University Frankfurt, Germany; Luoyang Wang, Qingdao University, China Edited by: Ines Zidi, Tunis El Manar University, Tunisia |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2023.1202098 |