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Understanding Glioblastoma Tumor-Associated Macrophages

Glioblastoma cells.

One of the significant contributors to glioblastoma, a cancer of the brain and one of the most aggressive malignancies, tumor-associated macrophages have great potential as therapeutic targets; however, targeting these cells has not been effective, in part due to a limited understanding of the reasons behind their behavior. Researchers seeking to better understand this behavior have now discovered that tumor-associated macrophages are composed of two cell types: brain-resident microglia and bone marrow-derived macrophages.

"In order to develop more effective immunotherapies to treat glioblastoma, we must first understand the properties of each of these macrophage populations individually rather than treating them as one homogenous entity," commented Zhihong Chen, PhD, Research Professor at New York University Shanghai and lead author of the study, which has now been published in Proceedings of the National Academy of Sciences of the United States of America.

To discover the differences between brain-resistant microglia and circulating bone marrow derived-monocytes, the researchers used high-resolution open-skull 2-photon microscopy on mouse models of glioblastoma and discovered that bone marrow-derived monocytes are smaller, minimally branched cells that move frequently compared with the larger, highly branched, motionless microglia cells. The investigators also found that the use of anti-vascular therapy in conjunction with antichemotaxis therapy successfully prohibited tumor-associated macrophage infiltration, in particular against bone marrow-derived monocytes.

"This research provides the scientific community with a novel mouse model to study the populations of glioblastoma-associated macrophages both separately and together," said the study's senior author, Dolores Hambardzumyan, PhD, Assistant Professor in the Department of Pediatrics at Emory University School of Medicine. "Our results also demonstrate the efficacy of blocking macrophage infiltration and calls for the use of combination therapies to enhance patients' survival."

For More Information

Chen Z, Ross JL & Hambardzumyan D (2019). Intravital 2-photon imaging reveals distinct morphology and infiltrative properties of glioblastoma-associated macrophages. Proc Natl Acad Sci U S A. [Epub ahead of print] DOI:10.1073/pnas.1902366116

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