Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression
Natalia Ochocka,
Pawel Segit,
Kamil Wojnicki,
Salwador Cyranowski,
Julian Swatler,
Karol Jacek,
Wiesława Grajkowska,
Bozena Kaminska
Affiliations
Natalia Ochocka
Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland
Pawel Segit
Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland
Kamil Wojnicki
Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland
Salwador Cyranowski
Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland; Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-109 Warsaw, Poland
Julian Swatler
Laboratory of Cytometry, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland
Karol Jacek
Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland
Wiesława Grajkowska
Department of Pathology, The Children’s Memorial Health Institute, 04-736 Warsaw, Poland
Bozena Kaminska
Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland; Corresponding author
Summary: 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/macrophages, 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.
