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.

Ebiomedicine
|February 4, 2018
PubMed
Abstract

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.

Related Concept Videos

Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
3.5K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.7K
Role of Hematopoietic Growth Factors01:28

Role of Hematopoietic Growth Factors

Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
4.0K
Factors Influencing Microbial Growth: pH01:29

Factors Influencing Microbial Growth: pH

Microorganisms are classified as acidophiles, neutrophiles, or alkaliphiles based on their pH growth preferences, reflecting their adaptations to specific environments. Maintaining a stable intracellular pH is critical for macromolecular stability and enzymatic activity, which can be challenged by external pH variations.Neutrophiles, such as Escherichia coli, grow optimally between pH 5.5 and 8.0. These microorganisms inhabit neutral or slightly acidic environments and employ mechanisms like...
1.3K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
86.8K
Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.8K