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RUNX1/CD44 axis regulates the proliferation, migration, and immunotherapy of gliomas: A single-cell sequencing
Hao Zhang1, Hui Cao2,3, Hong Luo1
1Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Background:
Glioma is one of the most common, primary, and lethal adult brain tumors because of its extreme aggressiveness and poor prognosis. Several recent studies relevant to the immune function of CD44, a transmembrane glycoprotein as a significant hyaluronic acid receptor, have achieved great success, revealing the critical role of CD44 in immune infiltration in gliomas. The overexpression of CD44 has been verified to correlate with cancer aggressiveness and migration, while the clinical and immune features of CD44 expression have not yet been thoroughly characterized in gliomas.
Methods:
Molecular and clinical data of glioma collected from publicly available genomic databases were analyzed.
Results:
CD44 was up-expressed in malignant gliomas, notably in the 1p/19q non-codeletion cases, isocitrate dehydrogenase (IDH) wild-type, and mesenchymal subtypes in GBM samples. CD44 expression level strongly correlates with stromal and immune cells, mainly infiltrating the glioma microenvironment by single-cell sequencing analysis. Meanwhile, CD44 can be a promising biomarker in predicting immunotherapy responses and mediating the expression of PD-L1. Finally, RUNX1/CD44 axis could promote the proliferation and migration of gliomas.
Conclusions:
Therefore, CD44 was responsible for glioma growth and progression. It could potentially lead to a novel target for glioma immunotherapy or a prognostic biomarker.
Insights
CD44 is overexpressed in aggressive gliomas, correlating with immune cell infiltration and predicting immunotherapy response. This transmembrane glycoprotein is crucial for glioma progression and may serve as a novel therapeutic target.
Area of Science:
- Neuro-oncology
- Immunology
- Molecular Biology
Background:
- Glioma is a lethal adult brain tumor with poor prognosis.
- CD44, a transmembrane glycoprotein and hyaluronic acid receptor, plays a critical role in glioma immune infiltration.
- CD44 overexpression correlates with increased cancer aggressiveness and migration.
Purpose of the Study:
- To characterize the clinical and immune features of CD44 expression in gliomas.
- To investigate the role of CD44 in glioma progression and its potential as a therapeutic target.
Main Methods:
- Analysis of molecular and clinical data from public glioma genomic databases.
- Single-cell sequencing to analyze CD44 expression and its correlation with cellular components in the glioma microenvironment.
Main Results:
- CD44 is upregulated in malignant gliomas, particularly in 1p/19q non-codeletion, IDH-wildtype, and mesenchymal GBM subtypes.
- CD44 expression correlates with stromal and immune cell infiltration within the glioma microenvironment.
- CD44 shows potential as a biomarker for predicting immunotherapy response and mediating PD-L1 expression.
- The RUNX1/CD44 axis promotes glioma proliferation and migration.
Conclusions:
- CD44 significantly contributes to glioma growth, progression, and aggressiveness.
- CD44 represents a potential novel target for glioma immunotherapy and a prognostic biomarker.

