{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:09:57Z","timestamp":1788948597084,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008920","name":"University of Saskatchewan","doi-asserted-by":"publisher","award":["#426368"],"award-info":[{"award-number":["#426368"]}],"id":[{"id":"10.13039\/100008920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Comparative Oncology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Canine soft tissue sarcomas (STSs) are locally invasive tumours, making local recurrence a major clinical challenge. Time to recurrence (TTR) and associated immune factors remain poorly characterized. This study aimed to characterize the immune microenvironment of canine STS and identify factors associated with TTR. Medical records from 27 dogs with STS that recurred after surgery were reviewed. Histopathological, transcriptomic, and immunological analyses were performed in a tissue\u2010available subcohort of 20 dogs. Immune\u2010related gene expression was characterized using the NanoString canine IO panel. Tumour\u2010infiltrating immune cells and tertiary lymphoid structures (TLSs) were assessed immunohistochemically using CD3, CD20, and FoxP3. Associations with TTR were evaluated using Cox proportional hazards models and log\u2010rank tests. Median TTR was 358\u2009days. Age and tumour location were associated with TTR in univariable analyses of the full cohort, but neither age nor the overall location effect remained significant when analysed together. Higher NOD2 expression and Cluster 1 assignment were associated with shorter TTR across exploratory multivariable models. Cluster 1 tumours exhibited abundant lymphocyte infiltration and enrichment of immunosuppressive pathways, whereas Cluster 2 tumours demonstrated lower immune infiltration and proinflammatory signatures. TLS\u2010positive tumours had greater lymphocyte infiltration, with FoxP3+ cells accumulated within TLSs. Paired recurrent tumours contained significantly more large TLSs than primary tumours. Higher NOD2 expression and an immunologically active but suppressed tumour phenotype were associated with shorter TTR, whereas the association with anatomical location was model\u2010dependent. Regulatory T cells and TLSs may contribute to the immune landscape associated with local recurrence and warrant further investigation as potential therapeutic targets.<\/jats:p>","DOI":"10.1111\/vco.70111","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:49:56Z","timestamp":1788947396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Clinical and Immunological Factors of Local Recurrence in Canine Soft Tissue Sarcoma"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1328-3023","authenticated-orcid":false,"given":"Kazuki","family":"Mizuta","sequence":"first","affiliation":[{"name":"Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine University of Saskatchewan  Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Philibert","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, Western College of Veterinary Medicine University of Saskatchewan  Saskatoon Saskatchewan Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-5656","authenticated-orcid":false,"given":"Arata","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine University of Saskatchewan  Canada"},{"name":"Department of Clinical Studies, Ontario Veterinary Medicine College University of Guelph  Guelph Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-5827.2002.tb00066.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.5326\/0410241"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985810388820"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-950X.2014.12185.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.230.4.548"},{"issue":"1","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12917-019-1956-z","article-title":"Canine Myxosarcomas, a Retrospective Analysis of 32 Dogs (2003\u20132018)","volume":"15","author":"Iwaki Y.","year":"2019","journal-title":"BMC Veterinary Research"},{"key":"e_1_2_11_8_1","unstructured":"N.Postorino R.Berg B.Powers A.McChesney R.Taylor andS.Withrow Prognostic Variables for Canine Hemangiopericytoma: 50 Cases (1979\u20131984)(1988)."},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/030098588001700507"},{"issue":"9","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2460\/javma.23.01.0050","article-title":"Grade Shifts in Recurrent Canine Soft Tissue Sarcomas and Mast Cell Tumors","volume":"261","author":"Griffin M. A.","year":"2023","journal-title":"Journal of the American Veterinary Medical Association"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2000.tb02279.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.1997.211.09.1147"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-5827.2009.00809.x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.240.10.1181"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.13620"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17233860"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985820960131"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.12383"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985815591081"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2016.06.006"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2010.0557.x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2008.0179.x"},{"key":"e_1_2_11_23_1","unstructured":"American Kennel Club Dog Breeds by Size(2025) https:\/\/www.akc.org\/dog\u2010breeds\/."},{"key":"e_1_2_11_24_1","volume-title":"Surgical Pathology of Tumors of Domestic Animals: Tumors of Soft Tissue","author":"Roccabianca P.","year":"2020"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0256907"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.13020"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0713"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.489"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-950X.2008.00408.x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.2000.217.205"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2011.00822.x"},{"issue":"1","key":"e_1_2_11_32_1","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.1038\/s41467-023-39486-2","article-title":"The Proteomic Landscape of Soft Tissue Sarcomas","volume":"14","author":"Burns J.","year":"2023","journal-title":"Nature Communications"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1354\/vp.08-VP-0277-M-FL"},{"issue":"4","key":"e_1_2_11_34_1","first-page":"158","article-title":"Soft Tissue Sarcomas in Dogs: A Study Correlating Optimal Surgical Margin With Tumour Grade","volume":"34","author":"Banks T.","year":"2004","journal-title":"Australian Veterinary Practitioner"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901479"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1507"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.011"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2015.05.011"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1033704"},{"key":"e_1_2_11_40_1","unstructured":"\u201cAnimal and Plant Health Inspection Service \u201d USDA 165A\u2010979002(2025) https:\/\/www.aphis.usda.gov\/aphis\/ourfocus\/animalhealth\/veterinary\u2010biologics\/product\u2010summaries\/vet\u2010label\u2010data\/c8684f19\u201005d4\u201049e8\u20109e96\u2010c294acbac6ae."},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30624-1"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.07.018"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.1617"},{"issue":"1","key":"e_1_2_11_44_1","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1038\/s41467-018-05570-1","article-title":"Pan\u2010Cancer Deconvolution of Tumour Composition Using DNA Methylation","volume":"9","author":"Chakravarthy A.","year":"2018","journal-title":"Nature Communications"},{"issue":"4","key":"e_1_2_11_45_1","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.cell.2017.10.014","article-title":"Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas","volume":"171","author":"Lazar A. 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