Blood monocyte-derived CD169(+) macrophages contribute to antitumor immunity against glioblastoma

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Tumor-associated macrophages are believed to promote tumour progression and to hamper immune therapy in gliomas. Here authors identify a distinct population of macrophages within the glioblastoma immune microenvironment with antitumour properties and clearly distinguishable phenotypes and gene expression patterns from tumour promoting macrophages. Infiltrating tumor-associated macrophages (TAM) are known to impede immunotherapy against glioblastoma (GBM), however, TAMs are heterogeneous, and there are no clear markers to distinguish immunosuppressive and potentially immune-activating populations. Here we identify a subset of CD169(+) macrophages promoting an anti-tumoral microenvironment in GBM. Using single-cell transcriptome analysis, we find that CD169(+) macrophages in human and mouse gliomas produce pro-inflammatory chemokines, leading to the accumulation of T cells and NK cells. CD169 expression on macrophages facilitates phagocytosis of apoptotic glioma cells and hence tumor-specific T cell responses. Depletion of CD169(+) macrophages leads to functionally impaired antitumor lymphocytes and poorer survival of glioma-bearing mice. We show that NK-cell-derived IFN-gamma is critical for the accumulation of blood monocyte-derived CD169(+) macrophages in gliomas. Our work thus identifies a well-distinguished TAM subset promoting antitumor immunity against GBM, and identifies key factors that might shift the balance from immunosuppressive to anti-tumor TAM.
Publisher
NATURE PORTFOLIO
Issue Date
2022-10
Language
English
Article Type
Article
Citation

NATURE COMMUNICATIONS, v.13, no.1

ISSN
2041-1723
DOI
10.1038/s41467-022-34001-5
URI
http://hdl.handle.net/10203/299243
Appears in Collection
MSE-Journal Papers(저널논문)
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