PD-L1 Clones and Their Relevance in Glioblastoma, IDH-Wildtype: A Comparative Analysis

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Authors

HENDRYCH Michal VÁŇA František HERMANOVÁ Markéta LAKOMÝ Radek KAZDA Tomáš MATULOVÁ Květoslava HOMOLOVÁ Alena JELÍNKOVÁ Martina JANČÁLEK Radim SMRČKA Martin VYBÍHAL Václav ŠÁNA Jiří

Year of publication 2025
Type Article in Periodical
Magazine / Source Bratislava Medical Journal
MU Faculty or unit

Faculty of Medicine

Citation
web https://link.springer.com/article/10.1007/s44411-025-00245-y
Doi https://doi.org/10.1007/s44411-025-00245-y
Keywords Immunotherapy; Glioblastoma; PD-L1; SP263; 22C3; Biomarker
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Description Glioblastoma, IDH-wildtype (GBM), is the most common primary brain cancer and is associated with a poor prognosis. Anti-PD-L1 immune checkpoint inhibitors have shown promising results in other solid tumors, prompting studies evaluating their potential in GBM. Accurately determining programmed death-ligand 1 (PD-L1) expression, using different antibody clones, is essential for assessing the potential efficacy of immunotherapy in GBM patients. However, the variability in immunohistochemical expression of different PD-L1 clones in GBM has not been tested. This study aims to assess and compare PD-L1 expression using two antibody clones SP263 and 22C3 in a retrospective GBM cohort. PD-L1 testing yielded spatial variability within the same tumor sample and significant discordance between the tested PD-L1 assays with the SP263 clone consistently detecting higher PD-L1 positivity. Overall, 46.5% of GBM cases were PD-L1 positive (? 5%) with SP263, compared to 32.6% with 22C3. The inter-clone kappa agreement reached 0.71. Positive cases (? 5%) were 53.8% and 38.5% in the unmethylated MGMT GBM subgroup with SP263 and 22C3 respectively, while 35.3% or 23.5% in the methylated MGMT GBMs. Our findings underscore that commonly used PD-L1 assays yield discordant results, highlighting the need to establish a gold standard for PD-L1 testing as a predictive biomarker.
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