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IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization

Author

Listed:
  • Moritz F. Eissmann

    (La Trobe University)

  • Christine Dijkstra

    (La Trobe University)

  • Andrew Jarnicki

    (University of Melbourne)

  • Toby Phesse

    (La Trobe University
    European Cancer Stem Cell Research Institute and Cardiff University)

  • Jamina Brunnberg

    (La Trobe University
    Goethe University Frankfurt)

  • Ashleigh R. Poh

    (La Trobe University)

  • Nima Etemadi

    (La Trobe University
    University of Melbourne)

  • Evelyn Tsantikos

    (Monash University)

  • Stefan Thiem

    (La Trobe University)

  • Nicholas D. Huntington

    (University of Melbourne)

  • Margaret L. Hibbs

    (Monash University)

  • Alex Boussioutas

    (University of Melbourne)

  • Michele A. Grimbaldeston

    (University of South Australia and SA Pathology
    Genentech Inc.)

  • Michael Buchert

    (La Trobe University)

  • Robert J. J. O’Donoghue

    (La Trobe University
    University of Melbourne)

  • Frederick Masson

    (La Trobe University
    University Toulouse III, CHU Purpan)

  • Matthias Ernst

    (La Trobe University)

Abstract

The contribution of mast cells in the microenvironment of solid malignancies remains controversial. Here we functionally assess the impact of tumor-adjacent, submucosal mast cell accumulation in murine and human intestinal-type gastric cancer. We find that genetic ablation or therapeutic inactivation of mast cells suppresses accumulation of tumor-associated macrophages, reduces tumor cell proliferation and angiogenesis, and diminishes tumor burden. Mast cells are activated by interleukin (IL)-33, an alarmin produced by the tumor epithelium in response to the inflammatory cytokine IL-11, which is required for the growth of gastric cancers in mice. Accordingly, ablation of the cognate IL-33 receptor St2 limits tumor growth, and reduces mast cell-dependent production and release of the macrophage-attracting factors Csf2, Ccl3, and Il6. Conversely, genetic or therapeutic macrophage depletion reduces tumor burden without affecting mast cell abundance. Therefore, tumor-derived IL-33 sustains a mast cell and macrophage-dependent signaling cascade that is amenable for the treatment of gastric cancer.

Suggested Citation

  • Moritz F. Eissmann & Christine Dijkstra & Andrew Jarnicki & Toby Phesse & Jamina Brunnberg & Ashleigh R. Poh & Nima Etemadi & Evelyn Tsantikos & Stefan Thiem & Nicholas D. Huntington & Margaret L. Hib, 2019. "IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10676-1
    DOI: 10.1038/s41467-019-10676-1
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    Cited by:

    1. Yunpei Xu & Shaokai Wang & Qilong Feng & Jiazhi Xia & Yaohang Li & Hong-Dong Li & Jianxin Wang, 2024. "scCAD: Cluster decomposition-based anomaly detection for rare cell identification in single-cell expression data," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Yunxuan Lei & Xin Guo & Yanping Luo & Xiaoyin Niu & Yebin Xi & Lianbo Xiao & Dongyi He & Yanqin Bian & Yong Zhang & Li Wang & Xiaochun Peng & Zhaojun Wang & Guangjie Chen, 2024. "Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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