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Updated: Aug 13, 2026
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Expression of Fas ligand by microglia: possible role in glioma immune evasion
B Badie1, J Schartner, S Prabakaran
1Neuro-oncology Laboratory, Department of Neurological Surgery, University of Wisconsin School of Medicine, K3/805 Clinical Science Center, 600 Highland Ave., Madison, WI 53792-3232, USA. badie@neurosurg.wisc.edu
Abstract:
The immune-privileged status of the central nervous system is thought to limit the application of immunotherapy for treatment of malignant brain tumors. Because the Fas pathway has been proposed to play a role in immune evasion, we examined the effect of tumor environment on the expression of Fas ligand (FasL) in a mouse glioma model. Immunoblotting revealed the expression of membrane-bound FasL to nearly double when murine G26 gliomas were propagated intracranially (IC) as compared to subcutaneously (SC). Further analysis by flow cytometry revealed microglia, which were absent in the SC tumors, to account for half of the FasL expression in the IC tumors. Interestingly, when FasL activity was inhibited in IC tumors, the proportion of tumor-infiltrating leukocytes increased three-fold, reaching the same frequency as the SC tumors. These observations suggest that microglia are a major source of FasL expression in brain tumors and possibly contribute to the local immunosuppressive milieu of malignant gliomas.
Insights
Microglia in brain tumors significantly increase Fas ligand (FasL) expression, contributing to immune evasion. Inhibiting FasL boosts anti-tumor immune cell infiltration, suggesting new therapeutic strategies for malignant gliomas.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- The central nervous system's immune privilege limits brain tumor immunotherapy.
- The Fas pathway is implicated in immune evasion within the tumor microenvironment.
Purpose of the Study:
- To investigate the impact of the tumor environment on Fas ligand (FasL) expression in a mouse glioma model.
- To determine the cellular source of FasL in intracranial tumors.
Main Methods:
- Murine G26 gliomas were propagated intracranially (IC) and subcutaneously (SC).
- Immunoblotting and flow cytometry were used to analyze FasL expression.
- FasL activity was inhibited in IC tumors to assess its effect on immune cell infiltration.
Main Results:
- Intracranial G26 gliomas exhibited nearly double the membrane-bound FasL expression compared to subcutaneous gliomas.
- Microglia, absent in SC tumors, accounted for approximately 50% of FasL expression in IC tumors.
- Inhibition of FasL activity in IC tumors led to a three-fold increase in tumor-infiltrating leukocytes.
Conclusions:
- Microglia are a primary source of FasL in brain tumors.
- FasL expressed by microglia contributes to the immunosuppressive milieu of malignant gliomas.
- Targeting the Fas pathway may enhance anti-tumor immune responses in brain tumors.
