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Updated: Jun 15, 2026
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Systemic immune suppression in glioblastoma: the interplay between CD14+HLA-DRlo/neg monocytes, tumor factors, and
Michael P Gustafson1, Yi Lin, Kent C New
1Division of Transfusion Medicine, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905, USA.
Abstract:
Patients with glioblastoma (GBM) exhibit profound systemic immune defects that affect the success of conventional and immune-based treatments. A better understanding of the contribution of the tumor and/or therapy on systemic immune suppression is necessary for improved therapies, to monitor negative effects of novel treatments, to improve patient outcomes, and to increase understanding of this complex system. To characterize the immune profile of GBM patients, we phenotyped peripheral blood and compared these to normal donors. In doing so, we identified changes in systemic immunity associated with both the tumor and dexamethasone treated tumor bearing patients. In particular, dexamethasone exacerbated tumor associated lymphopenia primarily in the T cell compartment. We have also identified unique tumor and dexamethasone dependent altered monocyte phenotypes. The major population of altered monocytes (CD14(+)HLA-DR(lo/neg)) had a phenotype distinct from classical myeloid suppressor cells. These cells inhibited T cell proliferation, were unable to fully differentiate into mature dendritic cells, were associated with dexamethasone-mediated changes in CCL2 levels, and could be re-created in vitro using tumor supernatants. We provide evidence that tumors express high levels of CCL2, can contain high numbers of CD14(+) cells, that tumor supernatants can transform CD14(+)HLA-DR(+) cells into CD14(+)HLA-DR(lo/neg) immune suppressors, and that dexamethasone reduces CCL2 in vitro and is correlated with reduction of CCL2 in vivo. Consequently, we have developed a model for tumor mediated systemic immune suppression via recruitment and transformation of CD14(+) cells.
Insights
Glioblastoma (GBM) causes immune defects. Tumor cells and dexamethasone create immunosuppressive monocytes (CD14(+)HLA-DR(lo/neg)) that inhibit T cells, worsening immune suppression in GBM patients.
Area of Science:
- Immunology
- Oncology
- Neuro-oncology
Background:
- Glioblastoma (GBM) is associated with significant systemic immune dysfunction.
- Understanding the mechanisms of immune suppression in GBM is crucial for developing effective treatments.
- Therapies, including dexamethasone, can further impact the immune system in GBM patients.
Purpose of the Study:
- To characterize the systemic immune profile of glioblastoma patients.
- To investigate the effects of the tumor and dexamethasone on immune cells, particularly monocytes.
- To elucidate the mechanisms of tumor-mediated immune suppression in GBM.
Main Methods:
- Peripheral blood immune cell phenotyping in GBM patients and healthy donors.
- In vitro experiments using tumor supernatants to assess monocyte transformation.
- Analysis of cytokine levels (CCL2) in relation to tumor burden and dexamethasone treatment.
Main Results:
- GBM patients exhibit distinct systemic immune alterations compared to normal donors.
- Dexamethasone exacerbates T cell lymphopenia in GBM patients.
- A novel population of immunosuppressive monocytes (CD14(+)HLA-DR(lo/neg)) was identified, induced by tumor factors and modulated by dexamethasone.
- These monocytes inhibit T cell proliferation and dendritic cell differentiation.
Conclusions:
- Glioblastoma induces systemic immune suppression through the recruitment and transformation of monocytes.
- Dexamethasone alters immune cell profiles and may influence immunosuppressive monocyte populations.
- A model for tumor-mediated immune suppression involving CCL2 and CD14(+) monocytes is proposed.
