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
Review
. 2019 Jan 9:9:1503.
doi: 10.3389/fphar.2018.01503. eCollection 2018.

The Prognostic and Therapeutic Value of PD-L1 in Glioma

Ruo Qiao Chen  1 , Feng Liu  1   2 , Xin Yao Qiu  1   2 , Xiao Qian Chen  1   2
Affiliations
Review

The Prognostic and Therapeutic Value of PD-L1 in Glioma

Ruo Qiao Chen et al. Front Pharmacol. .

Abstract

Glioma is the most common type of primary brain tumors. After standard treatment regimen (surgical section, radiotherapy and chemotherapy), the average survival time remains merely around 14 months for glioblastoma (grade IV glioma). Recent immune therapy targeting to the immune inhibitory checkpoint axis, i.e., programmed cell death protein 1 (PD-1) and its ligand PD-L1 (i.e., CD274 or B7-H1), has achieved breakthrough in many cancers but still not in glioma. PD-L1 is considered a major prognostic biomarker for immune therapy in many cancers, with anti-PD-1 or anti-PD-L1 antibodies being used. However, the expression and subcellular distribution of PD-L1 in glioma cells exhibits great variance in different studies, severely impairing PD-L1's value as therapeutic and prognostic biomarker in glioma. The role of PD-L1 in modulating immune therapy is complicated. In addition, endogenous PD-L1 plays tumorigenic roles in glioma development. In this review, we summarize PD-L1 mRNA expression and protein levels detected by using different methods and antibodies in human glioma tissues in all literatures, and we evaluate the prognostic value of PD-L1 in glioma. We also summarize the relationships between PD-L1 and immune cell infiltration in glioma. The mechanisms regulating PD-L1 expression and the oncogenic roles of endogenous PD-L1 are discussed. Further, the therapeutic results of using anti-PD-1/PD-L1 antibodies or PD-L1 knockdown are summarized and evaluated. In summary, current results support that PD-L1 is not only a prognostic biomarker of immune therapy, but also a potential therapeutic target for glioma.

Keywords: PD-L1; Ras; glioma; immune response; tumor infiltrating lymphocytes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The regulation of PD-L1 expression in glioma cells. Red line indicates RNAs. PTEN-mu, PTEN-mutant; ER, endoplasmic reticulum.
Figure 2
Figure 2
The structure of PD-L1 protein molecule. The numbers represent the amino acid. Sig P, signal peptide; it directs PD-L1 toward cell membrane; TM, transmembrane domain; Cytoplasmic: the cytoplasmic or intracellular domain of PD-L1. The intracellular domain contains several conserved motifs: RMLDVEKC, DTSSK and QFEET.
Figure 3
Figure 3
The role of cell-intrinsic PD-L1 in modulating signaling pathway. Dashed lines: unknown mechanisms. →, induction or activation; →, binding.
See this image and copyright information in PMC

References

    1. Agata Y., Kawasaki A., Nishimura H., Ishida Y., Tsubata T., Yagita H., et al. (1996). Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int. Immunol. 8, 765–772. 10.1093/intimm/8.5.765 - DOI - PubMed
    1. Ahn B. J., Pollack I. F., Okada H. (2013). Immune-checkpoint blockade and active immunotherapy for glioma. Cancers (Basel) 5, 1379–1412. 10.3390/cancers5041379 - DOI - PMC - PubMed
    1. Almozyan S., Colak D., Mansour F., Alaiya A., Al-Harazi O., Qattan A., et al. (2017). PD-L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation. Int. J. Cancer 141, 1402–1412. 10.1002/ijc.30834 - DOI - PMC - PubMed
    1. Alsaab H. O., Sau S., Alzhrani R., Tatiparti K., Bhise K., Kashaw S. K., et al. (2017). PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front. Pharmacol. 8:561. 10.3389/fphar.2017.00561 - DOI - PMC - PubMed
    1. Ansell S. M., Lesokhin A. M., Borrello I., Halwani A., Scott E. C., Gutierrez M., et al. (2015). PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's Lymphoma. N. Engl. J. Med. 372, 311–319. 10.1056/NEJMoa1411087 - DOI - PMC - PubMed