IL-33 promotes gastric tumour growth in concert with activation and recruitment of inflammatory myeloid cells.

Autor:	Tran CP; Tumour Immunology Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Scurr M; Tumour Immunology Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., O'Connor L; Tumour Immunology Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Buzzelli JN; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia., Ng GZ; Mucosal Immunology Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Chin SCN; Tumour Immunology Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Stamp LA; Department of Anatomy and Physiology, The University of Melbourne, Victoria, Australia., Minamoto T; Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan., Giraud AS; Tumour Immunology Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia., Judd LM; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia., Sutton P; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.; Mucosal Immunology Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Co-senior authors., Menheniott TR; Tumour Immunology Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.; Mucosal Immunology Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Co-senior authors.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2022 Jun 01; Vol. 13, pp. 785-799. Date of Electronic Publication: 2022 Jun 01 (Print Publication: 2022).
DOI:	10.18632/oncotarget.28238
Abstrakt:	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. Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare. (Copyright: © 2022 Tran et al.)
Databáze:	MEDLINE
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