Related Experiment Video
Updated: Dec 23, 2025
Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
Immune involvement of the contralateral hemisphere in a glioblastoma mouse model
Matheus H W Crommentuijn1, Sjoerd T T Schetters2, Sophie A Dusoswa2
1Department of Molecular Cell Biology and Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands m.crommentuijn@amsterdamumc.nl y.vankooyk@amsterdamumc.nl.
Background:
Glioblastoma (GBM) is the most common and deadliest form of brain cancer in adults. Standard treatment, consisting of surgery and radiochemotherapy, only provides a modest survival benefit and is incapable of combating infiltrating GBM cells in other parts of the brain. New therapies in clinical trials, such as anti-programmed cell death 1 immunotherapy, have so far shown limited success in GBM. Moreover, it is unclear how the growth of GBM suppresses the immune system locally at the site of the brain tumor or if distant sites of tumor cell migration are also involved. Invasive GBM cells in brain tissue beyond the primary tumor limit the use of surgery, thus immunotherapy could be beneficial if activated/suppressed immune cells are present in the contralateral hemisphere.
Methods:
Here, we used a syngeneic orthotopic GL26 GBM mouse model and multiparameter fluorescence-activated cell sorting analysis to study the phenotype of resident and infiltrating immune cells in both the brain tumor hemisphere and contralateral hemisphere.
Results:
We show that lymphoid cells, including tumor antigen-specific CD8+ tumor-infiltrating lymphocytes (TILs) are present in the tumor and are characterized by a tolerogenic phenotype based on high immune checkpoint expression. Massive infiltration of myeloid cells is observed, expressing immune checkpoint ligands, suggesting an immune-dependent coinhibitory axis limiting TIL responses. Surprisingly, these phenotypes are paralleled in the contralateral hemisphere, showing that infiltrating immune cells are also present at distant sites, expressing key immune checkpoints and immune checkpoint ligands.
Conclusion:
Whole-brain analysis indicates active immune involvement throughout the brain, both at the site of the primary tumor and in the contralateral hemisphere. Using the right combination and timing, immune checkpoint blockade could have the potential to activate immune cells at the site of the brain tumor and at distant sites, thereby also targeting diffusely infiltrating GBM cells.
Insights
Glioblastoma immune cells in the tumor and distant brain areas show suppressive traits. Immune checkpoint blockade may activate these cells, potentially treating infiltrating brain cancer cells.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer research
Background:
- Glioblastoma (GBM) is a deadly brain cancer with limited treatment options.
- Current therapies like surgery and radiochemotherapy offer modest survival benefits.
- The immune suppressive mechanisms of GBM, both local and distant, remain unclear.
Purpose of the Study:
- To investigate the phenotype of immune cells within the brain tumor and contralateral hemisphere in a GBM mouse model.
- To understand how GBM influences the immune system throughout the brain.
Main Methods:
- Utilized a syngeneic orthotopic GL26 Glioblastoma mouse model.
- Employed multiparameter fluorescence-activated cell sorting (FACS) for immune cell analysis.
- Examined immune cell phenotypes in both tumor and contralateral hemispheres.
Main Results:
- Tumor-infiltrating lymphocytes (TILs) in the tumor exhibited a tolerogenic phenotype with high immune checkpoint expression.
- Myeloid cells infiltrated the tumor, expressing immune checkpoint ligands that suppressed TIL responses.
- Surprisingly, similar immune cell phenotypes and distant immune cell infiltration were observed in the contralateral hemisphere.
Conclusions:
- Active immune involvement occurs throughout the brain in GBM, including distant sites.
- Immune checkpoint blockade presents a potential strategy to activate immune cells both locally and distantly.
- Targeting these immune cells could offer a new approach to combat infiltrating GBM cells.
