{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:28:02Z","timestamp":1790803682679,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,2,19]],"date-time":"2018-02-19T00:00:00Z","timestamp":1518998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["20305"],"award-info":[{"award-number":["20305"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>Tertiary lymphoid structures (TLSs) display phenotypic and functional characteristics of secondary lymphoid organs, and often develop in tissues affected by chronic inflammation, as well as in certain inflammation\u2010associated cancers where they are prognostic of improved patient survival. However, the mechanisms that govern the development of tumour\u2010associated TLSs remain ill\u2010defined. Here, we observed tumour\u2010associated TLSs in a preclinical mouse model (<jats:italic>gp130<\/jats:italic><jats:sup>F\/F<\/jats:sup>) of gastric cancer, where tumourigenesis is dependent on hyperactive STAT3 signalling through the common IL\u20106 family signalling receptor, gp130. Gastric tumourigenesis was associated with the development of B and T cell\u2010rich submucosal lymphoid aggregates, containing CD21<jats:sup>+<\/jats:sup> cellular networks and high endothelial venules. Temporally, TLS formation coincided with the development of gastric adenomas and induction of homeostatic chemokines including <jats:italic>Cxcl13<\/jats:italic>, <jats:italic>Ccl19<\/jats:italic> and <jats:italic>Ccl21<\/jats:italic>. Reflecting the requirement of gp130\u2010driven STAT3 signalling for gastric tumourigenesis, submucosal TLS development was also STAT3\u2010dependent, but independent of the cytokine IL\u201017 which has been linked with lymphoid neogenesis in chronic inflammation and autoimmunity. Interestingly, upregulated lymphoid chemokine expression and TLS formation were also observed in a chronic gastritis model induced by <jats:italic>Helicobacter felis<\/jats:italic> infection. Tumour\u2010associated TLSs were also observed in patients with intestinal\u2010type gastric cancer, and a gene signature linked with TLS development in <jats:italic>gp130<\/jats:italic><jats:sup>F\/F<\/jats:sup> mice was associated with advanced clinical disease, but was not prognostic of patient survival. Collectively, our <jats:italic>in vivo<\/jats:italic> data reveal that hyperactive gp130\u2010STAT3 signalling closely links gastric tumourigenesis with lymphoid neogenesis, and while a TLS gene signature was associated with advanced gastric cancer in patients, it did not indicate a favourable prognosis.<\/jats:p>","DOI":"10.1002\/ijc.31298","type":"journal-article","created":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T08:48:55Z","timestamp":1518079735000},"page":"167-178","source":"Crossref","is-referenced-by-count":52,"title":["Hyperactive gp130\/STAT3\u2010driven gastric tumourigenesis promotes submucosal tertiary lymphoid structure development"],"prefix":"10.1002","volume":"143","author":[{"given":"David G.","family":"Hill","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity Systems Immunity Research Institute, School of Medicine, Cardiff University Cardiff Wales United 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Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"West","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Oshima","sequence":"additional","affiliation":[{"name":"Division of Genetics Cancer Research Institute, Kanazawa University Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"McLeod","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Oshima","sequence":"additional","affiliation":[{"name":"Division of Genetics Cancer Research Institute, Kanazawa University Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awen","family":"Gallimore","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity Systems Immunity Research Institute, School of Medicine, Cardiff University Cardiff Wales United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley","family":"D'Costa","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prithi S.","family":"Bhathal","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Sievert","sequence":"additional","affiliation":[{"name":"Department of Medicine Monash Medical Centre, Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Biomedicine Discovery Institute, Department of Microbiology Monash University Clayton VIC 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