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Updated: Jun 29, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Astrocytic regulation of human monocytic/microglial activation
Alex M Kostianovsky1, Lisa M Maier, Richard C Anderson
1Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Recent reports have described reduced immunological responsiveness and stimulatory capacity among monocytes/microglia that infiltrate malignant human gliomas. Herein, we demonstrate that culture of ex vivo human monocytes or primary human microglia with tumor cells isolated from glioblastoma multiforme (GBM) specimens renders them tolerogenic, capable of suppressing the function of ex vivo monocytes in the absence of tumor cells or their soluble factors. We demonstrate that the tolerance induced in monocytes/microglia by GBM tumor cells is not associated with interference with the signaling cascade associated with TLR- or CD40-induced monocyte activation. Rather, these tumor cells appear to up-regulate pathways that antagonize positive signaling pathways, including but not limited to STAT3 and STAT5. Finally, we demonstrate that the tolerogenic properties of GBM tumor cells amplify properties inherent to nontransformed astrocytes. Future studies that identify all of the molecular mechanisms by which astrocytes and malignant gliomas suppress monocyte/microglial function will have dual therapeutic benefits: suppressing these pathways may benefit patients with astrocytic tumors, while enhancing them may benefit patients with autoimmune processes within the CNS, such as multiple sclerosis.
Insights
Glioblastoma tumor cells induce immune tolerance in monocytes and microglia. This immune suppression involves specific signaling pathways, offering potential therapeutic targets for brain tumors and autoimmune diseases.
Area of Science:
- Neuroscience
- Immunology
- Oncology
Background:
- Monocytes and microglia infiltrating gliomas exhibit reduced immune function.
- Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor.
Purpose of the Study:
- To investigate how glioblastoma tumor cells affect the immune functions of monocytes and microglia.
- To identify the molecular mechanisms underlying GBM-induced immune tolerance.
Main Methods:
- Co-culture of human monocytes/microglia with primary glioblastoma tumor cells.
- Analysis of monocyte activation signaling pathways (e.g., TLR, CD40).
- Investigation of STAT3 and STAT5 signaling in tolerogenic monocytes/microglia.
Main Results:
- Glioblastoma tumor cells induce a tolerogenic phenotype in monocytes and microglia.
- This tolerance suppresses monocyte function independently of tumor cells or soluble factors.
- GBM-induced tolerance does not inhibit TLR- or CD40-mediated activation but upregulates antagonistic pathways like STAT3/STAT5.
- Tolerogenic properties of GBM cells are amplified by astrocytes.
Conclusions:
- Glioblastoma tumor cells actively induce immune tolerance in myeloid cells.
- Targeting STAT3/STAT5 pathways could offer therapeutic strategies for astrocytic tumors.
- Enhancing these pathways may benefit patients with central nervous system autoimmune diseases like multiple sclerosis.
