| First Author | Tran CP | Year | 2022 |
| Journal | Oncotarget | Volume | 13 |
| Pages | 785-799 | PubMed ID | 35677533 |
| Mgi Jnum | J:326621 | Mgi Id | MGI:7315925 |
| Doi | 10.18632/oncotarget.28238 | Citation | Tran CP, et al. (2022) IL-33 promotes gastric tumour growth in concert with activation and recruitment of inflammatory myeloid cells. Oncotarget 13:785-799 |
| abstractText | Interleukin-33 (IL-33) is an IL-1 family cytokine known to promote T-helper (Th) type 2 immune responses that are often deregulated in gastric cancer (GC). IL-33 is overexpressed in human gastric tumours suggesting a role in driving GC progression although a causal link has not been proven. Here, we investigated the impact of IL-33 genetic deficiency in the well-characterized gp130 (F/F) mouse model of GC. Expression of IL-33 (and it's cognate receptor, ST2) was increased in human and mouse GC progression. IL-33 deficient gp130 (F/F) /Il33 (-/-) mice had reduced gastric tumour growth and reduced recruitment of pro-tumorigenic myeloid cells including key mast cell subsets and type-2 (M2) macrophages. Cell sorting of gastric tumours revealed that IL-33 chiefly localized to gastric (tumour) epithelial cells and was absent from tumour-infiltrating immune cells (except modest IL-33 enrichment within CD11b(+) CX3CR1(+)CD64(+)MHCII(+) macrophages). By contrast, ST2 was absent from gastric epithelial cells and localized exclusively within the (non-macrophage) immune cell fraction together with mast cell markers, Mcpt1 and Mcpt2. Collectively, we show that IL-33 is required for gastric tumour growth and provide evidence of a likely mechanism by which gastric epithelial-derived IL-33 drives mobilization of tumour-promoting inflammatory myeloid cells. |
