{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:03:10Z","timestamp":1785402190083,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022664","name":"Universidad de Le\u00f3n","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100022664","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02tzt0b78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The canine transmissible venereal tumor (TVT) is a neoplasm of the external genitalia of dogs, considered one of four reported contagious tumors in animals. These tumors have different presentations, with steady, progressive, or regressive stages. In some areas of Mexico, where the prevalence of TVT is high (5.15%), two morphological types are usually observed: one steady, pedunculated, strawberry-like (Type A) and one progressive, multilobulated, cauliflower-like (Type B). This study aimed to characterize the histopathological and inflammatory infiltrate patterns in eight stray dogs showing both morphological types of natural TVT (n = 4 each), to identify potential differences between tumor morphologies. Histopathological and immunohistochemical techniques were applied to tumor samples to evaluate the interaction between pathological morphology and the following cell markers: ionized calcium-binding adaptor molecule 1 (IBA1) for activated macrophages (including resident macrophages), inducible nitric oxide synthase (iNOS) for M1 macrophages, CD163 for M2 macrophages, CD3 for T lymphocytes, CD20 for B lymphocytes, and lambda light chain for plasma cells. The results showed a greater inflammatory infiltrate in Type A tumors than in Type B ones, with a parallel increase in activated macrophages and B lymphocytes. The presence of M1 and M2 macrophages was scarce in both types of tumors, and T lymphocytes were almost absent. This study reveals a stronger and more balanced local immune response in dogs with Type A TVTs compared with Type B tumors, which may underlie differences in tumor characteristics, although individual tumor heterogeneity should be considered.<\/jats:p>","DOI":"10.3390\/ani16081262","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:01:22Z","timestamp":1776686482000},"page":"1262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differences in Histopathology and Local Immune Response in Steady and Progressive Natural Transmissible Venereal Tumors in Mexican Dogs"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2931-4033","authenticated-orcid":false,"given":"Ileana Zorhaya","family":"Mart\u00ednez-Ramos","sequence":"first","affiliation":[{"name":"Facultad de Medicina Veterinaria y Zootecnia, Universidad Popular Aut\u00f3noma del Estado de Puebla, Puebla 72410, Mexico"},{"name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n del Estado de Puebla, Puebla 72400, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5865-5845","authenticated-orcid":false,"given":"Diego","family":"P\u00e9rez-Maroto","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5027-3072","authenticated-orcid":false,"given":"Natalia","family":"Garc\u00eda-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2431-5029","authenticated-orcid":false,"given":"Patricia","family":"Barroso","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9859-8391","authenticated-orcid":false,"given":"Adan","family":"Garc\u00eda Balbuena","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Veterinaria y Zootecnia, Universidad Popular Aut\u00f3noma del Estado de Puebla, Puebla 72410, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6731-9759","authenticated-orcid":false,"given":"Guadalupe","family":"N\u00fa\u00f1ez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Veterinaria y Zootecnia, Universidad Popular Aut\u00f3noma del Estado de Puebla, Puebla 72410, Mexico"},{"name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n del Estado de Puebla, Puebla 72400, Mexico"},{"name":"Facultad de Medicina Veterinaria y Zootecnia No. 2. Universidad Aut\u00f3noma de Guerrero, Cuajinicuilapa 41940, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1461-1852","authenticated-orcid":false,"given":"Mar\u00eda Benedicta","family":"Bottini Luzardo","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Veterinaria y Zootecnia No. 2. Universidad Aut\u00f3noma de Guerrero, Cuajinicuilapa 41940, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0679-8661","authenticated-orcid":false,"given":"Juan Francisco","family":"Garc\u00eda Mar\u00edn","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5121-7264","authenticated-orcid":false,"given":"Ana","family":"Balseiro","sequence":"additional","affiliation":[{"name":"Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"},{"name":"Departamento de Sanidad Animal, Instituto de Ganader\u00eda de Monta\u00f1a (IGM-CSIC), 24346 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/vco.12060","article-title":"Canine Transmissible Venereal Tumour: A Review","volume":"14","author":"Ganguly","year":"2013","journal-title":"Vet. Comp. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/age.13260","article-title":"Canine Transmissible Venereal Tumor\u2014From General to Molecular Characteristics: A Review","volume":"54","author":"Faro","year":"2023","journal-title":"Anim. Genet."},{"key":"ref_3","unstructured":"Maxie, M.G. (2016). Female Genital System. Pahology of Domestic Animals (Volume 3), Elsevier."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Strakova, A., and Murchison, E.P. (2014). The Changing Global Distribution and Prevalence of Canine Transmissible Venereal Tumour. BMC Vet. Res., 10.","DOI":"10.1186\/s12917-014-0168-9"},{"key":"ref_5","unstructured":"Maxie, M.G. (2016). Male Genital System. Pathology of Domestic Animals (Volume 3), Elsevier."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1939-165X.2006.tb00097.x","article-title":"Cutaneous Transmissible Venereal Tumor without Genital Involvement in a Prepubertal Female Dog","volume":"35","author":"Marcos","year":"2006","journal-title":"Vet. Clin. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1046\/j.1439-0442.2001.00361.x","article-title":"Primary Intranasal Transmissible Venereal Tumour in the Dog: A Retrospective Study of Six Spontaneous Cases","volume":"48","author":"Papazoglou","year":"2001","journal-title":"J. Vet. Med. Ser. A Physiol. Pathol. Clin. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1748-5827.2000.tb03187.x","article-title":"Brain and Ocular Metastases from a Transmissible Venereal Tumour in a Dog","volume":"41","author":"Ferreira","year":"2000","journal-title":"J. Small Anim. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100929","DOI":"10.1016\/j.tcam.2024.100929","article-title":"Evaluation of Canine and Feline Tumors in Morocco: Results of a Prospective Observational Study of 250 Cases (2020\u20132023)","volume":"63","author":"Laissaoui","year":"2024","journal-title":"Top. Companion Anim. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/bjc.1981.220","article-title":"Canine Transmissible Venereal Sarcoma: Distribution of T and B Lymphocytes in Blood, Draining Lymph Nodes and Tumours at Different Stages of Growth","volume":"44","author":"Chandler","year":"1981","journal-title":"Br. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s11259-006-3309-1","article-title":"Canine Transmissible Venereal Tumour: Asessment of Mast Cell Numbers as Indicators of the Growth Phase","volume":"30","author":"Mukaratirwa","year":"2006","journal-title":"Vet. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.vetimm.2009.01.002","article-title":"Effects of Immunotherapy of IL-6 and IL-15 Plasmids on Transmissible Venereal Tumor in Beagles","volume":"130","author":"Chou","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.vetimm.2010.10.013","article-title":"Immunopathogenic Behaviors of Canine Transmissible Venereal Tumor in Dogs Following an Immunotherapy Using Dendritic\/Tumor Cell Hybrid","volume":"139","author":"Pai","year":"2011","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1023\/A:1006491918910","article-title":"Review of Canine Transmissible Venereal Sarcoma","volume":"24","author":"Das","year":"2000","journal-title":"Vet. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"92","DOI":"10.4102\/jsava.v80i2.178","article-title":"Combination Therapy Using Intratumoral Bacillus Calmette-Guerin (BCG) and Vincristine in Dogs with Transmissible Venereal Tumours: Therapeutic Efficacy and Histological Changes","volume":"80","author":"Mukaratirwa","year":"2009","journal-title":"J. S. Afr. Vet. Assoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.tvjl.2008.11.009","article-title":"Predictive Factors for the Regression of Canine Transmissible Venereal Tumor during Vincristine Therapy","volume":"183","author":"Scarpelli","year":"2010","journal-title":"Vet. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/vco.13038","article-title":"Clinical Guidelines for Canine Transmissible Venereal Tumour Treatment: Systematic Review and Meta-Analysis","volume":"23","author":"Pimentel","year":"2025","journal-title":"Vet. Comp. Oncol."},{"key":"ref_18","unstructured":"Moulton, J.E. (1990). Tumors of the Genital Systems. Tumors in Domestic Animals, University of California Press."},{"key":"ref_19","first-page":"1117","article-title":"Stromal Cells and Extracellular Matrix","volume":"19","author":"Mukaratirwa","year":"2004","journal-title":"Histo. Histopathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0165-2427(03)00032-1","article-title":"Canine Transmissible Venereal Tumor Cell Depletion of B Lymphocytes: Molecule(s) Specifically Toxic for B Cells","volume":"92","author":"Liao","year":"2003","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s00262-007-0446-5","article-title":"Interactions of Host IL-6 and IFN-\u03b3 and Cancer-Derived TGF-\u03921 on MHC Molecule Expression during Tumor Spontaneous Regression","volume":"57","author":"Hsiao","year":"2008","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s00262-007-0386-0","article-title":"Transient Downregulation of Monocyte-Derived Dendritic-Cell Differentiation, Function, and Survival during Tumoral Progression and Regression in an in Vivo Canine Model of Transmissible Venereal Tumor","volume":"57","author":"Liu","year":"2008","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_23","first-page":"e2651","article-title":"Prevalencia y Distribuci\u00f3n de Tumor Ven\u00e9reo Transmisible En Perros de Una Comunidad Rural En M\u00e9xico","volume":"27","author":"Villalobos","year":"2022","journal-title":"Rev. MVZ C\u00f3rdoba"},{"key":"ref_24","unstructured":"R Core Team (2020). R: A Language and Environment for Statistical Computing, R Core Team."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.cell.2006.05.051","article-title":"Clonal Origin and Evolution of a Transmissible Cancer","volume":"126","author":"Murgia","year":"2006","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/imm.12377","article-title":"Immunology of Naturally Transmissible Tumours","volume":"144","author":"Siddle","year":"2014","journal-title":"Immunology"},{"key":"ref_27","first-page":"1","article-title":"C\u00e9lulas Presentadoras De Ant\u00edgeno: C\u00e9lulas Dendr\u00edticas Y Su Papel En La Lengua Azul","volume":"23","author":"Pedrera","year":"2010","journal-title":"Real Acad. Cienc. Vet. Andal. Orient."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.cellimm.2013.07.008","article-title":"Role of AIF-1 in the Regulation of Inflammatory Activation and Diverse Disease Processes","volume":"284","author":"Zhao","year":"2013","journal-title":"Cell. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6218","DOI":"10.12659\/MSM.908510","article-title":"Expression of Allograft Inflammatory Factor-1 (AIF-1) in Hepatocellular Carcinoma","volume":"24","author":"Zhang","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pan, Y., Yu, Y., Wang, X., and Zhang, T. (2020). Tumor-Associated Macrophages in Tumor Immunity. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.583084"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0165-2427(98)00131-7","article-title":"Immunohistochemical Study of the Local Inflammatory Infiltrate in Spontaneous Canine Transmissible Venereal Tumour at Different Stages of Growth","volume":"64","author":"Day","year":"1998","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.rvsc.2022.02.020","article-title":"Cell-Mediated Immunity and Expression of MHC Class I and Class II Molecules in Dogs Naturally Infected by Canine Transmissible Venereal Tumor: Is There Complete Spontaneous Regression Outside the Experimental CTVT?","volume":"145","author":"Romagnoli","year":"2022","journal-title":"Res. Vet. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1590\/s0100-736x2016000900009","article-title":"Immunocytochemical Characterization of Primary Cell Culture in Canine Transmissible Venereal Tumor","volume":"36","author":"Ballestero","year":"2016","journal-title":"Pesqui. Veterin\u00e1ria Bras."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e20200082","DOI":"10.1590\/0103-8478cr20200082","article-title":"Do Alterations in Gene Expressions Influence Tumorigenesis in the Transmissible Venereal Tumor in Dogs?","volume":"50","author":"Yamatogi","year":"2020","journal-title":"Ci\u00eancia Rural"},{"key":"ref_35","first-page":"447","article-title":"Spontaneous Canine Transmissible Venereal Tumor: Cell Morphology and Influence on P-Glycoprotein Expression","volume":"34","author":"Gaspar","year":"2010","journal-title":"Turk. J. Vet. Anim. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/ar.23527","article-title":"Canine Transmissible Venereal Tumor: Is Its Biological Behavior Changing?","volume":"300","author":"Duzanski","year":"2017","journal-title":"Anat. Rec."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"111044","DOI":"10.1016\/j.vetimm.2025.111044","article-title":"Transcriptomic Signatures of Cytomorphological Heterogeneity in Canine Transmissible Venereal Tumor","volume":"292","year":"2026","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1002\/eji.201545497","article-title":"Innate Immune Memory: Implications for Host Responses to Damage-Associated Molecular Patterns","volume":"46","author":"Crisan","year":"2016","journal-title":"Eur. J. Immunol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/8\/1262\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:36:16Z","timestamp":1776832576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/8\/1262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ani16081262"],"URL":"https:\/\/doi.org\/10.3390\/ani16081262","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}