Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression

Malignant gliomas are aggressive, hard-to-treat brain tumors. Their tumor microenvironment is massively infiltrated by myeloid cells, mostly brain-resident microglia, bone marrow (BM)-derived monocytes/macro-phages, and dendritic cells that support tumor progression. Single-cell omics studies significantly dissected immune cell heterogeneity, but dynamics and specific functions of individual subpopulations were poorly recognized. We use Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) to precisely dissect myeloid cell identities and functionalities in murine GL261 gliomas. We demonstrate that the diversity of myeloid cells infiltrating gliomas is dictated by cell type and cell state. Glioma-activated microglia are the major source of cytokines attracting other immune cells, whereas BM-derived cells show the monocyte-to-macrophage transition in the glioma microenvironment. This transition is coupled with a phenotypic switch from the IFN-related to antigen-presentation and tumor-supportive gene expression. Moreover, we found sex-dependent differences in transcriptional programs and composition of myeloid cells in murine and human glioblastomas.

Automated summary

Malignant gliomas are aggressive brain tumors infiltrated by myeloid cells, including microglia and monocytes/macrophages, which support tumor progression. Using CITE-seq, we identified cell diversity and functionalities in murine gliomas. Glioma-activated microglia are major cytokine sources and BM-derived cells transition to tumor-supportive macrophages. We also found sex-dependent differences in myeloid cell programs and composition in murine and human glioblastomas.