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

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. Hibbs, Alex Boussioutas, Michele A. Grimbaldeston, Michael Buchert, Robert J. J. O’Donoghue, Frederick Masson and Matthias Ernst ()
Additional contact information
Moritz F. Eissmann: La Trobe University
Christine Dijkstra: La Trobe University
Andrew Jarnicki: University of Melbourne
Toby Phesse: La Trobe University
Jamina Brunnberg: La Trobe University
Ashleigh R. Poh: La Trobe University
Nima Etemadi: La Trobe University
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
Michael Buchert: La Trobe University
Robert J. J. O’Donoghue: La Trobe University
Frederick Masson: La Trobe University
Matthias Ernst: La Trobe University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10676-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10676-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-10676-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().