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Updated: Feb 15, 2026

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
Published on: September 11, 2015
Radiotherapy Upregulates Programmed Death Ligand-1 through the Pathways Downstream of Epidermal Growth Factor
Xing Song1, Yingjie Shao2, Tianwei Jiang1
1Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou 213003, China.
Background:
In the present study, we aimed to investigate the role of epidermal growth factor receptor (EGFR) pathway in the up-regulation of programmed death ligand-1 (PD-L1) caused by radiotherapy (RT).
Materials And Methods:
Tissue microarrays (TMA) consisting of glioma cancer specimens from 64 patients were used to examine the correlation between PD-L1 and EGFR levels. Furthermore, we performed in vitro experiments to assess the role of EGFR pathway in RT-upregulated PD-L1 expression using human glioma cell lines U87 and U251.
Results:
Our data demonstrated that the PD-L1 expression was significantly correlated with EGFR expression in glioma specimens (χ2=5.00, P=0.025). The expressions of PD-L1 at the protein and mRNA levels were both significantly up-regulated by RT (P<0.05). The expressions of phosphorylated EGFR and janus kinase 2 (JAK2) were also induced by RT (P<0.05). Besides, inhibition of EGFR pathway could abrogate the RT-triggered PD-L1 up-regulation (P>0.05). The combination of RT with EGFR inhibitor exhibited the same effect on antitumor immune response compared with the combination of RT with PD-L1 neutralizing antibody (Ab).
Conclusions:
RT could up-regulate the PD-L1 expression through the pathways downstream of EGFR in glioma.
Insights
Radiotherapy up-regulates programmed death ligand-1 (PD-L1) in glioma by activating the epidermal growth factor receptor (EGFR) pathway. Inhibiting EGFR abrogates this effect, suggesting a therapeutic target for enhancing cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Radiotherapy (RT) can influence the tumor immune microenvironment.
- Programmed death ligand-1 (PD-L1) is a key immune checkpoint molecule.
- The epidermal growth factor receptor (EGFR) pathway is implicated in various cancers.
Purpose of the Study:
- To investigate the role of the EGFR pathway in RT-induced PD-L1 up-regulation in glioma.
- To explore the correlation between PD-L1 and EGFR expression in glioma specimens.
Main Methods:
- Analysis of tissue microarrays from 64 glioma patients to correlate PD-L1 and EGFR levels.
- In vitro experiments using U87 and U251 human glioma cell lines.
- Assessment of PD-L1, phosphorylated EGFR, and JAK2 expression following RT and EGFR inhibition.
Main Results:
- Significant correlation found between PD-L1 and EGFR expression in glioma (P=0.025).
- RT significantly up-regulated PD-L1, phosphorylated EGFR, and JAK2 expression (P<0.05).
- EGFR pathway inhibition abrogated RT-induced PD-L1 up-regulation, with comparable antitumor effects to PD-L1 blockade.
Conclusions:
- Radiotherapy up-regulates PD-L1 expression in glioma via pathways downstream of EGFR.
- Targeting the EGFR pathway presents a potential strategy to enhance RT efficacy in glioma treatment.
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