Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Jun 16;5(11):e1196310.
doi: 10.1080/2162402X.2016.1196310. eCollection 2016.

Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma

Zheng Wang  1 , Chuanbao Zhang  1 , Xing Liu  2 , Zhiliang Wang  1 , Lihua Sun  1 , Guanzhang Li  1 , Jingshan Liang  1 , Huimin Hu  2 , Yanwei Liu  1 , Wei Zhang  1 , Tao Jiang  3
Affiliations

Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma

Zheng Wang et al. Oncoimmunology. .

Abstract

Background: PD-L1 has been widely reported as immune check points in a range of malignancies as well as some immune-originated diseases. In glioma, the role of PD-L1 remains unclear. We aimed at investigating its role at transcriptome level and relationship with clinical practice. Method and patients: In total, 976 glioma samples with transcriptome data, including 301 microarray data from Chinese Glioma Genome Atlas (CGGA project) and 675 RNAseq data from TCGA project, were enrolled into our study. Clinical and IDH mutation data were also available. R language was used as the main tool for statistical analysis and graphical work. Results: PD-L1 expression was found to be positively correlated with WHO grade of glioma. PD-L1 seemed to express more in mesenchymal subtype according to TCGA transcriptional classification scheme and may contribute as a potential marker for mesenchymal subtype in glioblastoma. Pearson correlation test indicated that PD-L1 showed robust correlation with PD1, PD-L2, and CD80 in CGGA dataset. Subsequent gene ontology analysis based on significantly correlated genes of PD-L1 revealed that PD-L1 seemed to be profoundly associated with T cell activation. To further investigate the relationship between PD-L1 expression and immune response, we selected a series of immune signatures, which were then transformed into metagenes, and found that PD-L1 expression was particularly paralleled with T-cells and macrophages-related immune response instead of B cell linage-related immune response. In line with the corresponding biological process, PD-L1 exhibited predictive value for glioma patients: Higher PD-L1 indicated significantly shorter survival, especially in glioblastoma. Conclusion: PD-L1 is upregulated in glioblastoma, and is synergistic with other check point members. Moreover, PD-L1 is significantly associated with T-cell activation and macrophage-related immune response and predicts much worse survival for patients, warranting clinical trials of PD1/PD-L1 checkpoint inhibitors for potential glioma treatment.

Keywords: Checkpoint inhibitors; PD-L1; glioma; immune response.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
PD-L1 expression in CGGA (A) dataset and TCGA (B) data set according to IDH status. *** indicates p value< 0.001, * indicates p value < 0.05.
Figure 2.
Figure 2.
PD-L1 expression in molecular subtypes (A, B) and predictive value for mesenchymal subtype (C, D).
Figure 3.
Figure 3.
Correlation of PD-L1 homologs and family members in glioma (A, C) and GBM (B, D).
Figure 4.
Figure 4.
Correlation of check point members in glioma (A, C) and GBM (B, D).
Figure 5.
Figure 5.
Gene ontology analysis for PD-L1 in glioma.
Figure 6.
Figure 6.
PD-L1-related immune response.
Figure 7.
Figure 7.
Survival analysis for PD-L1.
See this image and copyright information in PMC

References

    1. Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA 2010; 60:166-93; PMID:20445000; http://dx.doi.org/ 10.3322/caac.20069 - DOI - PMC - PubMed
    1. Yang P, Zhang W, Wang Y, Peng X, Chen B, Qiu X, Li G, Li S, Wu C, Yao K et al.. IDH mutation and MGMT promoter methylation in glioblastoma: Results of a prospective registry. Oncotarget 2015; 6:40896-906; PMID:26503470; http://dx.doi.org/ 10.18632/oncotarget.5683 - DOI - PMC - PubMed
    1. Hussain SF, Yang D, Suki D, Aldape K, Grimm E, Heimberger AB. The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro Oncol 2006; 8:261-79; PMID:16775224; http://dx.doi.org/ 10.1215/15228517-2006-008 - DOI - PMC - PubMed
    1. Garofalo S, D'Alessandro G, Chece G, Brau F, Maggi L, Rosa A, Porzia A, Mainiero F, Esposito V, Lauro C et al.. Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice. Nat Commun 2015; 6:6623; PMID:25818172; http://dx.doi.org/ 10.1038/ncomms7623 - DOI - PMC - PubMed
    1. Rolle CE, Sengupta S, Lesniak MS. Mechanisms of immune evasion by gliomas. Adv Exp Med Biol 2012; 746:53-76; PMID:22639159; http://dx.doi.org/ 10.1007/978-1-4614-3146-6_5 - DOI - PubMed

Publication types

LinkOut - more resources