Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17212
Title: Interleukin 33 Signaling Restrains Sporadic Colon Cancer in an Interferon-γ-Dependent Manner.
Authors: Eissmann, Moritz F;Dijkstra, Christine;Wouters, Merridee A;Baloyan, David;Mouradov, Dmitri;Nguyen, Paul M;Davalos-Salas, Mercedes;Putoczki, Tracy L;Sieber, Oliver M;Mariadason, John M;Ernst, Matthias;Masson, Frederick
Affiliation: Cancer and Inflammation Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Oncogenic Transcription Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia
La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia
Issue Date: Apr-2018
EDate: 2018-02-20
Citation: Cancer immunology research 2018; 6(4): 409-421
Abstract: Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell death. The epithelium and stroma of the intestine express large amounts of IL33 and its receptor St2. IL33 is therefore continuously released during homeostatic turnover of the intestinal mucosa. Although IL33 can prevent colon cancer associated with inflammatory colitis, the contribution of IL33 signaling to sporadic colon cancer remains unknown. Here, we utilized a mouse model of sporadic colon cancer to investigate the contribution of IL33 signaling to tumorigenesis in the absence of preexisting inflammation. We demonstrated that genetic ablation of St2 enhanced colon tumor development. Conversely, administration of recombinant IL33 reduced growth of colon cancer cell allografts. In reciprocal bone marrow chimeras, the concurrent loss of IL33 signaling within radioresistant nonhematopoietic, and the radiosensitive hematopoietic, compartments was associated with increased tumor burden. We detected St2 expression within the radioresistant mesenchymal cell compartment of the colon whose stimulation with IL33 induced expression ofbona fideNF-κB target genes. Mechanistically, we discovered that St2 deficiency within the nonhematopoietic compartment coincided with increased abundance of regulatory T cells and suppression of an IFNγ gene expression signature, whereas IL33 administration triggered IFNγ expression by tumor allograft-infiltrating T cells. The decrease of this IFNγ gene expression signature was associated with more aggressive disease in human colon cancer patients, suggesting that lack of IL33 signaling impaired the generation of a potent IFNγ-mediated antitumor immune response. Collectively, our data reveal that IL33 functions as a tumor suppressor in sporadic colon cancer.Cancer Immunol Res; 1-13. ©2018 AACR.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17212
DOI: 10.1158/2326-6066.CIR-17-0218
PubMed URL: 29463593
Type: Journal Article
Appears in Collections:Journal articles

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