{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T17:22:12Z","timestamp":1751304132381,"version":"3.37.3"},"reference-count":88,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"F\u00f6rderlinie TEAMS Mittel zur F\u00f6rderung der Vernetzung zwischen Wissenschaftler\/-innen der Freien Universit\u00e4t Berlin"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Canine cutaneous histiocytoma (CCH) is a tumor that originates from dermal Langerhans cells and affects particularly young dogs. The common spontaneous regression of CCH makes it an interesting model in comparative oncology research. Previous studies have indicated that anti-tumor immune responses may be involved, but details remain speculative to date. Here, we asked which specific immuno-oncological dynamics underlie spontaneous regression of CCH on mRNA and protein levels. QuantSeq 3\u2032 mRNA sequencing with functional over-representation analysis and an nCounter RNA hybridization assay were employed on 21 formalin-fixed, paraffin-embedded CCH samples representing three different tumor stages (dataset information: <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE261387\">GSE261387<\/jats:uri>\u2014Immuno-Oncologic Profiling by Stage-Dependent Transcriptome and Proteome Analyses of Spontaneously Regressing Canine Cutaneous Histiocytoma\u2014OmicsDI). Nine additional samples were subjected to matrix-assisted laser desorption\/ionization mass spectrometry imaging (MALDI-MSI). Surprisingly, only minor stage-specific differences were found. When we investigated expression of B7 family ligands and CD28 family receptors holding co-stimulatory and -inhibitory functions, respectively, we found a higher abundance of CD80, CD86, CTLA4 and CD28, which may trigger a balanced activation of lymphocyte-mediated immune responses. CD80 and CD86 expressing cells were further quantified by <jats:italic>in situ<\/jats:italic> hybridization and compared with data from three cases of canine histiocytic sarcoma (HS), a malignant tumor variant originating from antigen-presenting interstitial dendritic cells. A stage-specific increase of CD80 expressing cells was recorded in CCH from the tumor bottom to the top, while CD86 was continuously and homogenously expressed at high levels. Overall expression of CD80 in CCH was similar to that in HS (73.3 \u00b1 37.4% <jats:italic>vs<\/jats:italic> 62.1 \u00b1 46.4%), while significantly more CD86 expressing tumor cells were found in CCH (94.7 \u00b1 10.3%) when compared to HS (57.6 \u00b1 11.0%). Our data suggest that major immuno-oncological pathways are not regulated during regression of CCH on the mRNA or protein levels as detectable by the methods used. Instead, our data provide further evidence supporting previous hypotheses towards a role of immune stimulatory B7 family ligands and CD28 family receptors in the regression of CCH.<\/jats:p>","DOI":"10.7717\/peerj.18444","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T12:54:35Z","timestamp":1732625675000},"page":"e18444","source":"Crossref","is-referenced-by-count":2,"title":["Immuno-oncologic profiling by stage-dependent transcriptome and proteome analyses of spontaneously regressing canine cutaneous histiocytoma"],"prefix":"10.7717","volume":"12","author":[{"given":"Alina K.","family":"Loriani Fard","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, Freie Universit\u00e4t Berlin, Institute of Veterinary Pathology, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0279-7482","authenticated-orcid":true,"given":"Alexander","family":"Haake","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Freie Universit\u00e4t Berlin, Institute of Veterinary Pathology, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8056-5065","authenticated-orcid":true,"given":"Vladimir","family":"Jovanovic","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Computer Science, Freie Universit\u00e4t Berlin, Bioinformatics Solution Center, Berlin, Germany"},{"name":"Institute for Biology, Freie Universit\u00e4t Berlin, Human Biology and Primate Evolution, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandro","family":"Andreotti","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Computer Science, Freie Universit\u00e4t Berlin, Bioinformatics Solution Center, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hummel","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medicine, Institute of Pathology, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1998-4033","authenticated-orcid":true,"given":"Benjamin-Florian","family":"Hempel","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Freie Universit\u00e4t Berlin, Veterinary Center for Resistance Research, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4502-0393","authenticated-orcid":true,"given":"Achim D.","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Freie Universit\u00e4t Berlin, Institute of Veterinary Pathology, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"issue":"1","key":"10.7717\/peerj.18444\/ref-1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nature Genetics"},{"issue":"3\u20134","key":"10.7717\/peerj.18444\/ref-2","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.vetimm.2007.06.007","article-title":"CCH cells are potent stimulators in the allogeneic mixed leucocyte reaction","volume":"119","author":"Baines","year":"2007","journal-title":"Veterinary Immunology and Immunopathology"},{"issue":"1","key":"10.7717\/peerj.18444\/ref-3","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1146\/annurev.immunol.18.1.767","article-title":"Immunobiology of dendritic 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