{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T15:33:43Z","timestamp":1756308823004,"version":"3.37.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Penn Vet Companion Animal Research Fund"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA016520","P30 CA016520","K08CA252619"],"award-info":[{"award-number":["P30 CA016520","P30 CA016520","K08CA252619"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Histiocytic sarcoma (HS) is a rare yet lethal malignancy with no established standard of care therapies. A lack of pre-clinical models limits our understanding of HS pathogenesis and identification of therapeutic targets. Canine HS shares multiple clinical and genetic similarities with human HS, supporting its use as a unique translational model. Prior studies have investigated the immunogenicity of HS. Although increased tumor infiltrating lymphocyte (TIL) density is associated with favorable outcomes in canine HS, virtually all canine patients eventually succumb to progressive disease consistent with ultimate failure of anti-tumor immunity. To investigate potential regulators of the immune tumor microenvironment (TME), we undertook a comparative transcriptional approach of three long-lived cases of canine pulmonary HS with heavy T cell infiltrate and three short-lived cases of splenic HS that lacked significant T cell inflammation and compared these data to corresponding grossly normal tissues from dogs undergoing necropsy. This comparison identified <jats:italic>PDCD1,<\/jats:italic> encoding the immune checkpoint PD-1, and <jats:italic>SPP1,<\/jats:italic> encoding the secreted pro-tumorigenic protein osteopontin, as positive differentially expressed genes (DEGs) in canine HS. <jats:italic>TXNIP,<\/jats:italic> encoding the tumor suppressor TXNIP, was the most significant negative DEG. Comparative transcriptomic studies revealed conservation of enriched (including <jats:italic>SPP1<\/jats:italic>) and depleted (including <jats:italic>TXNIP<\/jats:italic>) DEGs between canine and human HS patients. Immunohistochemistry demonstrated osteopontin in the TMEs of canine and human HS. Collectively, we uncover PD-1, osteopontin, and TXNIP as putative actionable targets in HS and further establish canine HS as a preclinical platform to screen novel immunotherapeutic approaches for this deadly disease.<\/jats:p>","DOI":"10.1007\/s00262-024-03908-x","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T10:04:35Z","timestamp":1735898675000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification of immune suppressor candidates utilizing comparative transcriptional profiling in histiocytic sarcoma"],"prefix":"10.1007","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3210-618X","authenticated-orcid":false,"given":"Jennifer A.","family":"Lenz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles\u2011Antoine","family":"Assenmacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austin","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert G.","family":"Maki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Andres","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Radaelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9830-3151","authenticated-orcid":false,"given":"Matthew J.","family":"Atherton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,3]]},"reference":[{"key":"3908_CR1","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1182\/blood-2017-10-812495","volume":"131","author":"A Kommalapati","year":"2018","unstructured":"Kommalapati A, Tella SH, Durkin M et al (2018) Histiocytic sarcoma: a population-based analysis of incidence, demographic disparities, and long-term outcomes. 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