{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:16:11Z","timestamp":1776878171077,"version":"3.51.2"},"reference-count":71,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["UIDB\/00276\/2020"],"award-info":[{"award-number":["UIDB\/00276\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["UIDB\/CVT\/00772\/2020"],"award-info":[{"award-number":["UIDB\/CVT\/00772\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Feline mammary carcinoma (FMC) exhibits aggressive behavior, with limited treatment options. Given the relevance of the PD-1\/PD-L1\/PD-L2 axis in human breast cancer immunotherapy, this study assessed PD-1 and its ligands in rare FMC histotypes (n = 48) using immunohistochemistry on tumor cells (TCs), intratumoral lymphocytes (iTILs), and stromal tumor-infiltrating lymphocytes (sTILs). PD-1 was expressed in 13% of TCs, 85% of iTILs, and 94% of sTILs, while PD-L1 was observed in 46% of TCs, 96% of iTILs, and 100% of sTILs. PD-L2 was expressed in 79% of TCs and 100% of both iTILs and sTILs, with PD-L1\/PD-L2 co-expression in 42% of TCs. Higher PD-1 IHC scores in TCs were associated with a less aggressive biological behavior; PD-L1 in iTILs was linked to skin ulceration, whereas PD-L2 in TCs was associated with its absence. Our findings highlight the relevance of the PD-1\/PD-L1\/PD-L2 immune checkpoint in rare FMC subtypes and support further investigation into checkpoint-blockade therapies.<\/jats:p>","DOI":"10.3390\/vetsci12080731","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T15:56:16Z","timestamp":1754409376000},"page":"731","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PD-1, PD-L1, and PD-L2 Expression as Predictive Markers in Rare Feline Mammary Tumors"],"prefix":"10.3390","volume":"12","author":[{"given":"Maria","family":"Franco","sequence":"first","affiliation":[{"name":"CIISA\u2014Center of Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisboa, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1912-1457","authenticated-orcid":false,"given":"Fernanda","family":"Seixas","sequence":"additional","affiliation":[{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"},{"name":"Veterinary Sciences Department, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), UTAD, 5000-801 Vila Real, Portugal"}]},{"given":"Maria dos Anjos","family":"Pires","sequence":"additional","affiliation":[{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"},{"name":"Veterinary Sciences Department, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), UTAD, 5000-801 Vila Real, Portugal"}]},{"given":"Anabela","family":"Alves","sequence":"additional","affiliation":[{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"},{"name":"Veterinary Sciences Department, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), UTAD, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-1739","authenticated-orcid":false,"given":"Andreia","family":"Santos","sequence":"additional","affiliation":[{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"},{"name":"ICBAS-UP, School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Animal Science and Study Centre\/Food and Agrarian Sciences and Technologies Institute (CECA\/ICETA), 4050-478 Porto, Portugal"}]},{"given":"Carla","family":"Marrinhas","sequence":"additional","affiliation":[{"name":"Centre for Investigation Vasco da Gama (CIVG), Department of Veterinary Sciences, Vasco da Gama University School, 3020-210 Coimbra, Portugal"},{"name":"Onevetgroup Hospital Veterin\u00e1rio do Baixo Vouga (HVBV), 3750-742 \u00c1gueda, Portugal"}]},{"given":"Hugo","family":"Vilhena","sequence":"additional","affiliation":[{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), UTAD, 5000-801 Vila Real, Portugal"},{"name":"ICBAS-UP, School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Centre for Investigation Vasco da Gama (CIVG), Department of Veterinary Sciences, Vasco da Gama University School, 3020-210 Coimbra, Portugal"}]},{"given":"Joana","family":"Santos","sequence":"additional","affiliation":[{"name":"DNAtech Veterinary Laboratory, 1649-038 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3922-3602","authenticated-orcid":false,"given":"Pedro","family":"Fa\u00edsca","sequence":"additional","affiliation":[{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), UTAD, 5000-801 Vila Real, Portugal"},{"name":"DNAtech Veterinary Laboratory, 1649-038 Lisboa, Portugal"},{"name":"Faculty of Veterinary Medicine, Universidade Lus\u00f3fona de Humanidades e Tecnologias, 1749-024 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8845-794X","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Dias-Pereira","sequence":"additional","affiliation":[{"name":"ICBAS-UP, School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde (LAQV), Rede de Qu\u00edmica e Tecnologia (REQUIMTE), University of Porto, 4050-453 Porto, Portugal"}]},{"given":"Adelina","family":"Gama","sequence":"additional","affiliation":[{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"},{"name":"Veterinary Sciences Department, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Animal and Veterinary Research Centre (CECAV), UTAD, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1909-4540","authenticated-orcid":false,"given":"Jorge","family":"Correia","sequence":"additional","affiliation":[{"name":"CIISA\u2014Center of Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisboa, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5765-576X","authenticated-orcid":false,"given":"Fernando","family":"Ferreira","sequence":"additional","affiliation":[{"name":"CIISA\u2014Center of Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisboa, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gameiro, A., Urbano, A., and Ferreira, F. 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