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Updated: Dec 23, 2025
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
Glioblastoma hijacks microglial gene expression to support tumor growth
Sybren L N Maas1,2, Erik R Abels1, Lieke L Van De Haar1
1Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Background:
Glioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain, survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Despite the presence of large numbers of microglia in glioblastoma, the tumors continue to grow, and these neuroimmune cells appear incapable of keeping the tumor in check. To understand this process, we analyzed gene expression in microglia interacting with glioblastoma cells.
Methods:
We used RNASeq of isolated microglia to analyze the expression patterns of genes involved in key microglial functions in mice with glioblastoma. We focused on microglia that had taken up tumor-derived EVs and therefore were within and immediately adjacent to the tumor.
Results:
We show that these microglia have downregulated expression of genes involved in sensing tumor cells and tumor-derived danger signals, as well as genes used for tumor killing. In contrast, expression of genes involved in facilitating tumor spread was upregulated. These changes appear to be in part EV-mediated, since intracranial injection of EVs in normal mice led to similar transcriptional changes in microglia. We observed a similar microglial transcriptomic signature when we analyzed datasets from human patients with glioblastoma.
Conclusion:
Our data define a microgliaGlioblastoma specific phenotype, whereby glioblastomas have hijacked gene expression in the neuroimmune system to favor avoiding tumor sensing, suppressing the immune response, clearing a path for invasion, and enhancing tumor propagation. For further exploration, we developed an interactive online tool at http://www.glioma-microglia.com with all expression data and additional functional and pathway information for each gene.
Insights
Glioblastomas reprogram brain immune cells (microglia) to promote tumor growth instead of fighting it. This immune evasion is mediated by tumor-derived extracellular vesicles and observed in human patients.
Area of Science:
- Neuro-oncology
- Immunology
- Genomics
Background:
- Glioblastomas are aggressive primary brain tumors.
- Microglia are brain immune cells that normally combat threats.
- Glioblastoma cells release extracellular vesicles (EVs) that interact with microglia.
Purpose of the Study:
- To investigate how glioblastoma influences microglia function.
- To analyze gene expression changes in microglia within the glioblastoma microenvironment.
Main Methods:
- RNA sequencing (RNASeq) of microglia from glioblastoma-bearing mice.
- Focus on microglia that have internalized tumor-derived EVs.
- Analysis of gene expression datasets from human glioblastoma patients.
Main Results:
- Microglia near glioblastomas show downregulated tumor-sensing and tumor-killing genes.
- Genes promoting tumor invasion and spread are upregulated in these microglia.
- EVs from glioblastoma induce similar gene expression changes in normal microglia.
- A similar microglial transcriptomic signature was found in human glioblastoma samples.
Conclusions:
- Glioblastomas induce a specific microglia phenotype that suppresses anti-tumor immunity.
- Tumor cells hijack microglia to avoid detection, dampen immune response, and facilitate invasion.
- An interactive online tool was created to explore the gene expression data.
