Cell Reports (Jan 2023)

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

Journal volume & issue
Vol. 42, no. 1
p. 111971

Abstract

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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.

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