IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization
- Author(s)
- Eissmann, MF; Dijkstra, C; Jarnicki, A; Phesse, T; Brunnberg, J; Poh, AR; Etemadi, N; Tsantikos, E; Thiem, S; Huntington, ND; Hibbs, ML; Boussioutas, A; Grimbaldeston, MA; Buchert, M; O'Donoghue, RJJ; Masson, F; Ernst, M;
- Details
- Publication Year 2019-06-21,Volume 10,Issue #1,Page 2735
- Journal Title
- Nature Communications
- Publication Type
- Journal Article
- 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.
- Publisher
- Springer Nature
- Research Division(s)
- Immunology
- PubMed ID
- 31227713
- Publisher's Version
- https://doi.org/10.1038/s41467-019-10676-1
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-019-10676-1- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-07-01 12:57:15
Last Modified: 2019-07-01 01:04:08