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Brain resident and infiltrating innate immune cells adapt a tumor-supportive phenotype in the glioma microenvironment. Flow cytometry analysis supported by a single-cell RNA sequencing study of human gliomas indicate considerable cell type heterogeneity. It remains disputable whether microglia and infiltrating macrophages have the same or distinct roles in supporting glioma progression. Here, we performed single-cell transcriptomics analyses of CD11b+ cells sorted from murine syngeneic gliomas, indicating distinct activity of microglia, infiltrating monocytes/macrophages and CNS border-associated macrophages. Our results demonstrate a previously immeasurable scale of molecular heterogeneity in the innate immune response in gliomas. We identified genes differentially expressed in activated microglia from glioma-bearing mice of different sex, and profound overexpression of the MHCII genes by male microglial cells, which we also observed in bulk human glioma samples. Sex-specific gene expression in microglia in the glioma microenvironment may be relevant to sex differences in incidence and outcomes of glioblastoma patients.

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