Monocyte - neutrophil interplay drives mesenchymal transition in GBM

Myeloid cells comprise the majority of immune cells in tumors, where their content and composition is not only driver mutation-specific, but also tumor type-dependent. While these cells are essential for shaping the tumor microenvironment, promoting tumor growth, and contributing to therapeutic resistance, targeting tumor-associated myeloid cells, including bone-marrow-derived monocytes and neutrophils, has not been successful. To eliminate monocyte recruitment, we employed CRISPR/Cas9-based methods to delete the region on murine chromosome 11 harboring the monocyte chemoattractant protein family (MCP) genes, Ccl2, Ccl7, Ccl8, Ccl12, and Ccl11, which we termed qMCP-KO. Using these qMCP-knockout mice in combination with genetically engineered mouse models (GEMM) of glioblastoma (GBM), we investigated myeloid infiltraion by sc-RNA seq. We found that when monocyte infiltraion was abolisehd, a compensatory influx of nuetrophil in these tumor occured. These neutrophil promote tumor growth by releasing TNF, contributing to tumor hypoxic responses and aggression. We induced de novo brain tumor in WT, qMCP-KO mice of both genders. We isolated brain tumor cells at the humane endstage of these mice and ran sc-RNA seq on these cells to compare their functional differences.