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Updated: Dec 13, 2025
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Profiling of patients with glioma reveals the dominant immunosuppressive axis is refractory to immune function
Martina Ott1, Karl-Heinz Tomaszowski2, Anantha Marisetty1
1Department of Neurosurgery.
Abstract:
In order to prioritize available immune therapeutics, immune profiling across glioma grades was conducted, followed by preclinical determinations of therapeutic effect in immune-competent mice harboring gliomas. T cells and myeloid cells were isolated from the blood of healthy donors and the blood and tumors from patients with glioma and profiled for the expression of immunomodulatory targets with an available therapeutic. Murine glioma models were used to assess therapeutic efficacy of agents targeting the most frequently expressed immune targets. In patients with glioma, the A2aR/CD73/CD39 pathway was most frequently expressed, followed by the PD-1 pathway. CD73 expression was upregulated on immune cells by 2-hydroxyglutarate in IDH1 mutant glioma patients. In murine glioma models, adenosine receptor inhibitors demonstrated a modest therapeutic response; however, the addition of other inhibitors of the adenosine pathway did not further enhance this therapeutic effect. Although adenosine receptor inhibitors could recover immunological effector functions in T cells, immune recovery was impaired in the presence of gliomas, indicating that irreversible immune exhaustion limits the effectiveness of adenosine pathway inhibitors in patients with glioma. This study illustrates vetting steps that should be considered before clinical trial implementation for immunotherapy-resistant cancers, including testing an agent's ability to restore immunological function in the context of intended use.
Insights
Immune profiling identified the A2aR/CD73/CD39 pathway as a key target in glioma. Adenosine receptor inhibitors showed limited efficacy due to immune exhaustion in gliomas, highlighting the need for better preclinical vetting.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Therapeutics
Background:
- Glioma treatment requires effective immune therapeutics.
- Prioritizing immunomodulatory targets is crucial for therapeutic development.
Purpose of the Study:
- To profile immune cells in glioma patients and preclinical models.
- To evaluate the therapeutic potential of targeting key immunomodulatory pathways.
Main Methods:
- Immune profiling of T cells and myeloid cells from glioma patients and healthy donors.
- Preclinical assessment of therapeutic agents in immune-competent murine glioma models.
- Analysis of immunomodulatory target expression and therapeutic efficacy.
Main Results:
- The A2aR/CD73/CD39 pathway was highly expressed in glioma, followed by the PD-1 pathway.
- Adenosine receptor inhibitors showed modest efficacy in murine models, with no added benefit from combination therapy.
- Immune recovery was hindered by glioma presence, suggesting immune exhaustion limits therapeutic effectiveness.
Conclusions:
- The A2aR/CD73/CD39 pathway is a promising target for glioma immunotherapy.
- Preclinical models indicate limitations of adenosine pathway inhibitors due to immune exhaustion.
- Vetting strategies should assess immune restoration capacity in the context of the tumor microenvironment.
