Related Experiment Video
Updated: Dec 20, 2025
08:19
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
6.3K
Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases
Lin Zhang1,2, Jun Yao1, Yongkun Wei1
1Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Science Translational Medicine
|May 29, 2020
Summary
Researchers discovered that immunosuppressive neutrophils infiltrate the brain, promoting brain metastasis. This process involves a modified protein, pY696-EZH2, which can be targeted to treat brain metastasis.
Area of Science:
- Oncology
- Immunology
- Neuroscience
Background:
- The brain's immune privilege historically obscured the role of immune cells in brain metastases.
- Understanding immune cell infiltration is crucial for developing effective brain metastasis treatments.
Purpose of the Study:
- To elucidate the mechanisms by which immune cells, specifically neutrophils, contribute to brain metastasis.
- To identify novel therapeutic targets for combating brain metastasis.
Main Methods:
- Analysis of immune cell populations within brain metastases.
- Investigation of the role of enhancer of zeste homolog 2 (EZH2) phosphorylation at tyrosine-696 (pY696).
- Utilizing mouse models to test therapeutic interventions targeting G-CSF and Src kinases.
Main Results:
- A subset of immunosuppressive neutrophils is recruited to the brain, facilitating metastasis.
- Phosphorylated EZH2 (pY696-EZH2) acts as a transcription factor, increasing c-JUN expression.
- c-JUN up-regulates granulocyte colony-stimulating factor (G-CSF), recruiting more immunosuppressive neutrophils.
- Blocking G-CSF or combining immune checkpoint blockade with Src inhibitors reduced brain metastasis in mouse models.
Conclusions:
- pY696-EZH2 drives brain metastasis by promoting the infiltration of immunosuppressive neutrophils.
- Targeting pY696-EZH2, G-CSF, or Src kinases offers a promising therapeutic strategy for brain metastasis.
