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Updated: Mar 10, 2026
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages
Ian Zhang1, Darya Alizadeh1, Junling Liang2
1Division of Neurosurgery, City of Hope Beckman Research Institute, Duarte, California, United States of America.
Abstract:
Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1+ cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1+, MG and MP. However, in contrast to MP and Gr1+ cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1+ cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors.
Insights
Tumor-associated microglia and macrophages show varied arginase 1 expression in gliomas. Tumor microenvironment factors, not just macrophages, influence microglia polarization and antitumor activity.
Area of Science:
- Neuro-oncology
- Immunology
- Cell Biology
Background:
- Microglia (MG) and macrophages (MPs) are key immune cells in glioma, influencing tumor progression through pro- and anti-inflammatory cytokine release.
- The balance of MG/MP polarization dictates their antitumor efficacy, making their functional states critical in glioma.
- Understanding MG/MP heterogeneity is vital for developing effective glioma immunotherapies.
Purpose of the Study:
- To investigate variations in microglia and macrophage polarization in gliomas.
- To explore the role of tumor microenvironmental factors in regulating MG/MP function.
- To assess arginase 1 (Arg1) expression patterns in tumor-associated myeloid cells.
Main Methods:
- Isolation of Gr1+ cells, including microglia and macrophages, from intracranial GL261 murine gliomas using Fluorescence-Activated Cell Sorting (FACS).
- Microarray analysis to evaluate gene expression profiles of isolated tumor-infiltrating myeloid cells.
- Confirmation of arginase 1 expression in human Glioblastoma Multiforme (GBM) samples.
Main Results:
- Arginase 1 (Arg1), an M2 marker, was highly expressed in tumor-associated Gr1+ cells, MG, and MPs.
- MG exhibited a delayed upregulation of Arg1 compared to MPs and Gr1+ cells, particularly in larger tumors.
- MP depletion did not inhibit MG polarization, suggesting tumor-specific factors directly influence MG Arg1 expression.
- In human GBM, Arg1+ cells were predominantly neutrophils, not macrophages.
Conclusions:
- Tumor-associated microglia and macrophages display distinct polarization states and functional heterogeneity within gliomas.
- Tumor microenvironmental factors play a significant role in directing microglia polarization and Arg1 upregulation.
- Findings highlight the complex immune landscape in gliomas and suggest potential therapeutic targets.
