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Updated: Nov 29, 2025
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Comprehensive analysis of inhibitory checkpoint ligand expression by glioblastoma cells
Laverne D Robilliard1,2, Jane Yu1,2, Akshata Anchan1,2
1Department of Molecular Medicine and Pathology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Abstract:
Glioblastoma is a highly aggressive brain malignancy commonly refractory to classical and novel chemo-, radio- and immunotherapies, with median survival times of ~15 months following diagnosis. Poor immunological responses exemplified by the downregulation of T-cell activity, and upregulation of immunosuppressive cells within the tumor microenvironment have limited the effectiveness of immunotherapy in glioblastoma to date. Here we show that glioblastoma cells express a large repertoire of inhibitory checkpoint ligands known to control effector T cell responses. Furthermore, flow cytometry analysis reveals that glioblastoma cells with an enhanced stem cell-like phenotype express several investigated ligands at significant levels on their cell surface. This reveals that glioblastoma stem-like cells express suppressive ligands with the potential of suppressing major T cell checkpoint receptors. With this information, it is now essential that we understand the relevance of this extensive repertoire of immune checkpoint ligands and their functional consequence on immune evasion in glioblastoma. This is necessary to develop effective immunotherapeutics and to be able to match treatment to patient, especially in the light of CheckMate 143.
Insights
Glioblastoma stem-like cells express immune checkpoint ligands that suppress T-cell activity, hindering immunotherapy effectiveness. Understanding these suppressive mechanisms is crucial for developing better glioblastoma treatments.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- Glioblastoma is an aggressive brain cancer with poor prognosis, often resistant to current therapies.
- Limited immunotherapy success in glioblastoma is linked to poor T-cell responses and a suppressive tumor microenvironment.
- Immune checkpoint proteins regulate T-cell activity and are targets for cancer immunotherapy.
Purpose of the Study:
- To investigate the expression of inhibitory immune checkpoint ligands on glioblastoma cells, particularly those with stem-like properties.
- To understand the potential of these ligands to mediate immune evasion in glioblastoma.
- To inform the development of novel immunotherapeutics for glioblastoma.
Main Methods:
- Analysis of inhibitory checkpoint ligand expression on glioblastoma cells.
- Flow cytometry to assess cell surface ligand expression, focusing on stem-like glioblastoma cells.
Main Results:
- Glioblastoma cells express a wide range of inhibitory checkpoint ligands.
- Glioblastoma stem-like cells exhibit significant surface expression of multiple suppressive ligands.
- These ligands can potentially inhibit major T-cell checkpoint receptors, contributing to immune evasion.
Conclusions:
- Glioblastoma stem-like cells actively suppress anti-tumor immunity through the expression of immune checkpoint ligands.
- Targeting these suppressive ligands may represent a promising strategy for enhancing glioblastoma immunotherapy.
- Further research is needed to elucidate the functional impact of these ligands on immune evasion and guide personalized treatment approaches.
