Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma

• DOI: 10.1073/pnas.1721434116
• Publication Date: 2019-01-03T01:44:29Z
• Authors: Gregor Hutter; Johanna Theruvath; Claus Moritz Graef; Michael Zhang; Matthew Kenneth S...; Eva Maria Manz; Mariko L. Bennett; Andrew Olson; Tej D. Azad; Rahul Sinha; Carmel Chan; Suzana Assad Kahn; Sharareh Gholamin; Christy Wilson; Gerald Grant; Joy He; Irving L. Weissman; Siddhartha S. Mitra; Samuel H. Cheshier
• Keywords: CD47; Brain tumor

Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the microenvironment. Hence, modulation reeducation of tumor-associated GBM considered promising antitumor strategy. Resident invading shown distinct origin function. Whereas yolk sac-derived reside brain, blood-derived monocytes invade central nervous system only under pathological conditions like formation. We recently showed that disruption SIRPα-CD47 signaling axis efficacious against various tumors including primarily by inducing phagocytosis. However, most effects are attributed recruited from periphery but role resident unknown. Here, we sought utilize model distinguish peripheral within GBM-TAM pool, using orthotopically xenografted, immunodeficient, syngeneic mouse models genetically color-coded (Ccr2RFP) (Cx3cr1GFP). show even absence phagocytizing (Ccr2RFP/RFP), effector cell phagocytosis response anti-CD47 blockade. Additionally, morphological transcriptional changes. Importantly, profile shows less an inflammatory which makes them target for clinical applications.