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Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Combating immunosuppression in glioma
Eleanor A Vega1, Michael W Graner, John H Sampson
1Duke University School of Medicine, Department of Surgery, Division of Neurosurgery, 221 Sands Building, Durham, NC 27710, USA.
Abstract:
Despite maximal therapy, malignant gliomas have a very poor prognosis. Patients with glioma express significant immune defects, including CD4 lymphopenia, increased fractions of regulatory T cells in peripheral blood and shifts in cytokine profiles from Th1 to Th2. Recent studies have focused on ways to combat immunosuppression in patients with glioma as well as in animal models for glioma. We concentrate on two specific ways to combat immunosuppression: inhibition of TGF-beta signaling and modulation of regulatory T cells. TGF-beta signaling can be interrupted by antisense oligonucleotide technology, TGF-beta receptor I kinase inhibitors, soluble TGF-beta receptors and antibodies against TGF-beta. Regulatory T cells have been targeted with antibodies against T-cell markers, such as CD25, CTLA-4 and GITR. In addition, vaccination against Foxp3 has been explored. The results of these studies have been encouraging; combating immunosuppression may be one key to improving prognosis in malignant glioma.
Insights
Combating immune suppression in malignant glioma patients by targeting TGF-beta signaling and regulatory T cells shows promise. These strategies may improve patient prognosis despite poor outcomes with current therapies.
Area of Science:
- Neuro-oncology
- Immunology
Background:
- Malignant gliomas have a poor prognosis despite maximal therapy.
- Patients exhibit immune defects, including CD4 lymphopenia and increased regulatory T cells, shifting cytokine profiles from Th1 to Th2.
Purpose of the Study:
- To explore strategies for combating immunosuppression in malignant glioma.
- Focus on inhibiting TGF-beta signaling and modulating regulatory T cells.
Main Methods:
- Inhibiting TGF-beta signaling via antisense oligonucleotides, kinase inhibitors, soluble receptors, or antibodies.
- Targeting regulatory T cells using antibodies against CD25, CTLA-4, GITR, or vaccination against Foxp3.
Main Results:
- Studies targeting immunosuppression have yielded encouraging results.
- Combating immune suppression is a potential key to improving malignant glioma prognosis.
Conclusions:
- Targeting TGF-beta signaling and regulatory T cells are promising strategies for malignant glioma.
- Overcoming immune suppression may enhance treatment outcomes for glioma patients.
