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

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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))

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.

Suggested Citation

  • Hyun-Jin Kim & Jang Hyun Park & Hyeon Cheol Kim & Chae Won Kim & In Kang & Heung Kyu Lee, 2022. "Blood monocyte-derived CD169+ macrophages contribute to antitumor immunity against glioblastoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34001-5
    DOI: 10.1038/s41467-022-34001-5
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    1. Ji Eun Oh & Norifumi Iijima & Eric Song & Peiwen Lu & Jonathan Klein & Ruoyi Jiang & Steven H. Kleinstein & Akiko Iwasaki, 2019. "Migrant memory B cells secrete luminal antibody in the vagina," Nature, Nature, vol. 571(7763), pages 122-126, July.
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