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Gata6+ resident peritoneal macrophages promote the growth of liver metastasis

Author

Listed:
  • Mokarram Hossain

    (University of Calgary
    University of Calgary
    Early Oncology, AstraZeneca)

  • Raymond Shim

    (University of Calgary
    University of Calgary)

  • Woo-Yong Lee

    (University of Calgary)

  • Arlene H. Sharpe

    (Blavatnik Institute, Harvard Medical School, and Evergrande Centre for Immunological Diseases, Harvard Medical School and Brigham and Women’s Hospital
    Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital)

  • Paul Kubes

    (University of Calgary
    University of Calgary
    University of Calgary)

Abstract

Emerging evidence suggests that resident macrophages within tissues are enablers of tumor growth. However, a second population of resident macrophages surrounds all visceral organs within the cavities and nothing is known about these GATA6+ large peritoneal macrophages (GLPMs) despite their ability to invade injured visceral organs by sensing danger signals. Here, we show that GLPMs invade growing metastases that breach the visceral mesothelium of the liver via the “find me signal”, ATP. Depleting GLPMs either by pharmacological or genetic tools, reduces metastases growth. Apoptotic bodies from tumor cells induces programmed cell death ligand 1 (PD-L1) upregulation on GLPMs which block CD8+ T cell function. Direct targeting of GLPMs by intraperitoneal but not intravenous administration of anti-PD-L1 reduces tumor growth. Thermal ablation of liver metastases recruits huge numbers of GLPMs and enables rapid regrowth of tumors. GLPMs contribute to metastatic growth and tumor recurrence.

Suggested Citation

  • Mokarram Hossain & Raymond Shim & Woo-Yong Lee & Arlene H. Sharpe & Paul Kubes, 2022. "Gata6+ resident peritoneal macrophages promote the growth of liver metastasis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32080-y
    DOI: 10.1038/s41467-022-32080-y
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    References listed on IDEAS

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    1. Irene Soncin & Jianpeng Sheng & Qi Chen & Shihui Foo & Kaibo Duan & Josephine Lum & Michael Poidinger & Francesca Zolezzi & Klaus Karjalainen & Christiane Ruedl, 2018. "The tumour microenvironment creates a niche for the self-renewal of tumour-promoting macrophages in colon adenoma," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    2. Charles P. Lai & Edward Y. Kim & Christian E. Badr & Ralph Weissleder & Thorsten R. Mempel & Bakhos A. Tannous & Xandra O. Breakefield, 2015. "Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    3. Sydney R. Gordon & Roy L. Maute & Ben W. Dulken & Gregor Hutter & Benson M. George & Melissa N. McCracken & Rohit Gupta & Jonathan M. Tsai & Rahul Sinha & Daniel Corey & Aaron M. Ring & Andrew J. Conn, 2017. "PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity," Nature, Nature, vol. 545(7655), pages 495-499, May.
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