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. 2021 Aug;147(8):2271-2280.
doi: 10.1007/s00432-021-03656-w. Epub 2021 May 8.

Integrated analysis of programmed cell death ligand 1 expression reveals increased levels in high-grade glioma

Dorothee Hölzl  1 , Georg Hutarew  1 , Barbara Zellinger  1 , Hans U Schlicker  1 , Christoph Schwartz  2 , Peter A Winkler  2 , Karl Sotlar  1 , Theo F J Kraus  3
Affiliations

Integrated analysis of programmed cell death ligand 1 expression reveals increased levels in high-grade glioma

Dorothee Hölzl et al. J Cancer Res Clin Oncol. 2021 Aug.

Abstract

Purpose: Gliomas are the most frequent primary brain tumors of adults. Despite intensive research, there are still no targeted therapies available. Here, we performed an integrated analysis of glioma and programmed cell death ligand 1 (PD-L1) in 90 samples including 58 glioma and 32 control brain tissues.

Methods: To identify PD-L1 expression in glioma, we performed immunohistochemical analysis of PD-L1 tumor proportion score (TPS) using the clinically valid PD-L1 22C3 antibody on 90 samples including controls and WHO grade I-IV gliomas.

Results: We found that PD-L1 is highly expressed in a subfraction of glioma cells. Analysis of PD-L1 levels in different glioma subtypes revealed a strong intertumoral variation of PD-L1 protein. Furthermore, we correlated PD-L1 expression with molecular glioma hallmarks such as MGMT-promoter methylation, IDH1/2 mutations, TERT promoter mutations and LOH1p/19q.

Conclusion: In summary, we found that PD-L1 is highly expressed in a subfraction of glioma, indicating PD-L1 as a potential new marker in glioma assessment opening up novel therapeutic approaches.

Keywords: Glioblastoma; Glioma; Molecularly targeted therapy; PD-L1; Programmed cell death ligand 1.

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Conflict of interest statement

None declared.

Figures

Fig. 1
Fig. 1
PD-L1 expression in healthy brain tissue and glioma. Analysis of 90 tissue samples showed no PD-L1 expression in healthy cortex (a, b) and white matter regions (c, d). There was no noteworthy PD-L1 expression in low grade glioma, i.e., WHO grade I pilocytic astrocytoma (e, f) and diffuse astrocytoma (g, h). In high grade glioma there was an uneven PD-L1 expression with strong intertumoral heterogeneity in WHO grade III anaplastic astrocytoma (i, j) and glioblastoma (k, l). Distinct PD-L1 TPS scores of all 90 analyzed samples is presented in m. CX cortex, WM white matter, PA pilocytic astrocytoma, DA diffuse astrocytoma, AA anaplastic astrocytoma, GBM glioblastoma. a–l Scale bar: 100 µm
Fig. 2
Fig. 2
Statistical analysis of PD-L1 expression. Statistical analysis of PD-L1 expression showed significant overexpression of PD-L1 in glioma compared with healthy cortex (a) and white matter (b). Analysis of WHO grade I, II, III and IV glioma showed significant overexpression in high grade glioblastoma compared with low grade diffuse glioma. Analysis of individual TPS showed PD-L1 expression in glioma showed TPS of ≥ 50% in 27% of gliomas, TPS of 25–50% in 12% of gliomas, TPS of 10–25% in 10% of gliomas, TPS of 5–10% in 2% of gliomas, TPS of 1–5% in 9% of gliomas, and TPS of < 1% in 40% of gliomas (c). a, b Indicated are mean and SEM. *p < 0.05, **p < 0.01
Fig. 3
Fig. 3
Integrated analysis of PD-L1 expression and molecular genetic hallmarks of glioma. Analysis of PD-L1 expression and IDH status showed higher expression of PD-L1 in IDH wild type compared to IDH R132H mutated glioma (a). In case of TERT promoter mutation there was higher PD-L1 expression in TERT C228T and C250T mutated glioma (b). Analysis of LOH 1p/19q showed higher expression of PD-L1 in gliomas without LOH 1p/19q (d). Analysis of MGMT promoter methylation showed higher expression of PD-L1 in methylated glioma (c). Indicated are mean and SEM. m methylated, u unmethylated; n.s. not significant (p > 0.05), *p < 0.05
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