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Published on: November 28, 2015
The network of immunosuppressive pathways in glioblastoma
Davide Mangani1, Michael Weller2, Patrick Roth2
1Laboratory of Molecular Neuro-Oncology, Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland.
Abstract:
Glioblastoma remains a fatal tumor despite increased knowledge regarding the complex signalling pathways that drive this devastating disease. Recently, immunotherapeutic approaches have shown remarkable and durable responses in various cancers including metastatic melanoma and advanced non-small cell lung cancer. So far, it remains unclear whether these immunotherapeutics may also work against glioblastoma and other tumors residing in the central nervous system. It is well known that patients with glioblastoma suffer from profound local immunosuppression that represents the major hurdle to overcome in the context of immunotherapy. Several studies have demonstrated that this immunosuppressive phenotype is orchestrated by glioma-derived membrane-bound and soluble factors as well as the particular microenvironment within the brain. Here, we discuss the molecular and cellular pathways involved in glioblastoma-mediated inhibition of the immune system and highlight possible treatment approaches aiming at reinvigorating anti-tumor immune responses.
Insights
Glioblastoma immunotherapy faces challenges due to local immunosuppression. This review explores glioblastoma
Area of Science:
- Neuro-oncology
- Cancer immunotherapy
- Tumor microenvironment
Background:
- Glioblastoma is a fatal brain tumor with complex driving pathways.
- Immunotherapy has shown success in other cancers like melanoma and lung cancer.
- The efficacy of immunotherapy in central nervous system tumors like glioblastoma is uncertain.
Purpose of the Study:
- To discuss glioblastoma-mediated immune inhibition pathways.
- To highlight potential immunotherapeutic strategies for glioblastoma.
- To address the challenge of local immunosuppression in glioblastoma.
Main Methods:
- Review of molecular and cellular pathways involved in glioblastoma-induced immunosuppression.
- Analysis of factors contributing to the immunosuppressive tumor microenvironment in the brain.
- Discussion of current research on overcoming immune evasion in glioblastoma.
Main Results:
- Glioblastoma patients exhibit profound local immunosuppression.
- Glioma-derived factors and the brain microenvironment orchestrate this immunosuppressive phenotype.
- Understanding these mechanisms is crucial for developing effective immunotherapies.
Conclusions:
- Local immunosuppression is a major barrier to glioblastoma immunotherapy.
- Targeting the molecular and cellular pathways of immune inhibition is essential.
- Reinvigorating anti-tumor immune responses holds promise for treating glioblastoma.
