Macrophage and T cell Interactions in the Brain Tumor Microenvironment Daniela F. Quail1, Robert L. Bowman2, Leila Akkari3, Jason T. Huse4, Eric C. Holland5, James C. Sutton6, Johanna A. Joyce7,* 1Goodman Cancer Research Centre, Montreal, QC, Canada; 2Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Netherlands Cancer Institute, Amsterdam, NH, Netherlands 4MD Anderson Cancer Center, Houston, TX, USA; 5Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 6Novartis Institutes for Biomedical Research, Emeryville, CA, USA; 7University of Lausanne, Lausanne, VD, Switzerland *Corresponding author
The brain tumor microenvironment (TME) is a critical regulator of primary and metastatic brain tumor progression. The unique properties of this organ require a specific framework for designing TME-targeted interventions. This includes consideration of brain-resident cell types, the blood-brain barrier, and various aspects of the immune-suppressive environment. We have recently shown that macrophages can be targeted using CSF-1R inhibitors in preclinical models of glioblastoma, but that acquired resistance eventually develops, mediated by CD8+ T cells in the TME. We have found that therapeutically targeting the CD8+ T cell - macrophage communication axis is sufficient to reduce the emergence of drug resistance to CSF-1R inhibitors. By developing a comprehensive understanding of the complex microenvironmental landscape of glioblastomas, and dissecting the relationship between different immune populations, we will expand the range of therapeutic strategies available to target this deadly disease.
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