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

Hyun-Jin Kim, Jang Hyun Park, Hyeon Cheol Kim, Chae Won Kim, In Kang and Heung Kyu Lee ()
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Hyun-Jin Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Jang Hyun Park: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Hyeon Cheol Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Chae Won Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
In Kang: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Heung Kyu Lee: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract 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-γ 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.

Date: 2022
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DOI: 10.1038/s41467-022-34001-5

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