{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:22:56Z","timestamp":1773667376962,"version":"3.50.1"},"reference-count":85,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100015900","name":"OVC Pet Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015900","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Comparative Oncology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Urothelial carcinoma (UC) is the most common urinary tumour in dogs. Despite a range of treatment options, prognosis remains poor in dogs. In people, breakthroughs with checkpoint inhibitors have established new standards of care for muscle\u2010invasive bladder cancer patients and elevated levels of programmed cell death protein 1 (PD\u20101) suggest immune checkpoint blockade may be a novel target for therapy. The goal of this study was to determine if canine UC patients express elevated levels of lymphocyte\u2010specific PD\u20101 and\/or urinary cytokine biomarkers compared to healthy dogs. Paired blood and urine were evaluated in 10 canine UC patients, five cystitis patients and 10 control dogs for lymphocyte\u2010specific PD\u20101 expression via flow cytometry and relative cytokine expression. In UC patients, PD\u20101 expression was significantly elevated on CD8<jats:sup>+<\/jats:sup> lymphocytes in urine samples. UC patients had a higher CD4:CD8 ratio in their urine compared to healthy dogs, however, there was no significant variation in the CD8:Treg ratio between any group. Cystitis patients had significantly elevated levels of CD4<jats:sup>+<\/jats:sup> T cells, CD8<jats:sup>+<\/jats:sup> T cells and Tregs in their blood samples compared to UC patients and healthy dogs. Cytokine analysis demonstrated significant elevations in urinary cytokines (granulocyte\u2010macrophage colony\u2010stimulating factor, interferon\u2010gamma [IFN\u2010\u03b3], interleukin (IL)\u20102, IL\u20106 IL\u20107, IL\u20108 and IL\u201015, IP\u201010, KC\u2010like, IL\u201018, monocyte chemoattractant protein\u20101 and tumour necrosis factor\u2010alpha). Several of these cytokines have been previously correlated with both lymphocyte\u2010specific PD\u20101 expression (IFN\u2010\u03b3, IL\u20102, IL\u20107 and IL\u201015) in muscle\u2010invasive urothelial carcinoma in humans. Our results provide evidence of urinary lymphocyte PD\u20101 expression and future studies could elucidate whether veterinary UC patients will respond favourably to anti\u2010PD\u20101 immune checkpoint inhibitor therapy.<\/jats:p>","DOI":"10.1111\/vco.12788","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T10:49:34Z","timestamp":1637318974000},"page":"427-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evaluation of lymphocyte\u2010specific programmed cell death protein 1 receptor expression and cytokines in blood and urine in canine urothelial carcinoma patients"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1311-5467","authenticated-orcid":false,"given":"Christopher J.","family":"Pinard","sequence":"first","affiliation":[{"name":"Department of Clinical Studies, Ontario Veterinary College University of Guelph  Guelph Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-8288","authenticated-orcid":false,"given":"Ashley A.","family":"Stegelmeier","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Ontario Veterinary College University of Guelph  Guelph Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byram W.","family":"Bridle","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Ontario Veterinary College University of Guelph  Guelph Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7965-7149","authenticated-orcid":false,"given":"Anthony J.","family":"Mutsaers","sequence":"additional","affiliation":[{"name":"Department of Clinical Studies, Ontario Veterinary College University of Guelph  Guelph Ontario Canada"},{"name":"Department of Biomedical Sciences, Ontario Veterinary College University of Guelph  Guelph Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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