TMIC-29. CHARACTERIZING THE ROLE OF TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 2 (TREM2)-EXPRESSING MICROGLIA/MACROPHAGES IN GLIOBLASTOMA

Abstract

Abstract The tumor microenvironment in glioblastoma (GBM) contains numerous cell types, notably a rich immune compartment dominated by myeloid cells, such as brain-resident microglia and infiltrating macrophages. However, current immunotherapies target lymphoid components like T cells, which are sparse in the brain and the tumors originating there. Therefore, immune checkpoint drugs designed for systemic cancers have not yielded significant benefits for patients with glioblastoma, and the efficacy of immunotherapy for central nervous system malignancies lags behind treatments for other solid tumors. Further understanding of the myeloid compartment is necessary for developing glioblastoma immunotherapies. Our recent single cell RNA-seq (scRNA-seq) analyses have identified microglial clusters that are enriched for antigen presentation and phagocytic gene expression modules. These clusters were restricted to microglia and macrophages seen only in glioma patients, but not in myeloid cells derived from non-glioma brain controls. Triggering receptor expressed on myeloid cells 2 (TREM2), a receptor abundant on microglia and vital for the detection and phagocytosis of pathogens, was highly expressed in these clusters. Because microglia expressing TREM2 play a protective role in neurodegenerative diseases like Alzheimer's disease, we examined the function of TREM2+ myeloid cells in GBM using mice lacking TREM2. Implantation of GL261 cells in TREM2-/- mice showed significantly reduced survival relative to wild-type mice, suggesting a protective role of TREM2+ myeloid cells in glioma. Data on immunophenotyping of glioma xenografts from WT and TREM2-/- mice brains using state of the art technologies (e.g. Cytek) will be presented. We conclude that TREM2 is a phagocytic immunoregulator in glioblastoma, manifesting anti-glioma properties to TREM2+ myeloid cells.