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Serum PD-1/PD-L1 levels, tumor expression and PD-L1 somatic mutations in HER2-positive and triple negative normal-like feline mammary carcinoma subtypes

dc.contributor.authorNascimento, Catarina
dc.contributor.authorUrbano, Ana Catarina
dc.contributor.authorGameiro, Andreia
dc.contributor.authorFerreira, João
dc.contributor.authorCorreia, Jorge Manuel de Jesus
dc.contributor.authorFerreira, Fernando
dc.date.accessioned2022-01-21T12:17:21Z
dc.date.available2022-01-21T12:17:21Z
dc.date.issued2020
dc.description© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).pt_PT
dc.description.abstractTumor microenvironment has gained great relevance due to its ability to regulate distinct checkpoints mediators, orchestrating tumor progression. Serum programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) levels were compared with healthy controls and with serum cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and tumor necrosis factor-alpha (TNF-α) levels in order to understand the role of PD-1/PD-L1 axis in cats with mammary carcinoma. PD-1 and PD-L1 expression was evaluated in tumor-infiltrating lymphocytes (TILs) and cancer cells, as the presence of somatic mutations. Results showed that serum PD-1 and PD-L1 levels were significantly higher in cats with HER2-positive (p = 0.017; p = 0.032) and triple negative (TN) normal-like mammary carcinomas (p = 0.004; p = 0.015), showing a strong positive correlation between serum CTLA-4 and TNF-α levels. In tumors, PD-L1 expression in cancer cells was significantly higher in HER2-positive samples than in TN normal-like tumors (p = 0.010), as the percentage of PD-L1-positive TILs (p = 0.037). PD-L1 gene sequencing identified two heterozygous mutations in exon 4 (A245T; V252M) and one in exon 5 (T267S). In summary, results support the use of spontaneous feline mammary carcinoma as a model for human breast cancer and suggest that the development of monoclonal antibodies may be a therapeutic strategy.pt_PT
dc.description.sponsorshipThis research was funded by Fundação para a Ciência e a Tecnologia (Portugal) through the projects PTDC/CVT-EPI/3638/2014 and CIISA-UIDP/CVT/00276/2020. C.N. is receipt of a PhD fellowship from University of Lisbon (ref.C00191r) and A.G. is receipt of a PhD fellowship from Fundação para a Ciência e a Tecnologia (ref. SFRH/BD/132260/2017).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCancers (Basel). 2020 May 28;12(6):1386. PMID: 32481540; PMCID: PMC7352561pt_PT
dc.identifier.doi10.3390/cancers12061386pt_PT
dc.identifier.eissn2072-6694
dc.identifier.urihttp://hdl.handle.net/10451/50909
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationCIISA-UIDP/CVT/00276/2020pt_PT
dc.relationDeveloping diagnostic tools for feline mammary carcinomas and improving chemotherapy based on HER2 and topoisometase status
dc.relation.publisherversionhttps://www.mdpi.com/journal/cancerspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCTLA-4pt_PT
dc.subjectPD-1pt_PT
dc.subjectPD-L1pt_PT
dc.subjectTNF-αpt_PT
dc.subjectBiomarkerspt_PT
dc.subjectFeline mammary carcinomapt_PT
dc.subjectImmunotherapypt_PT
dc.titleSerum PD-1/PD-L1 levels, tumor expression and PD-L1 somatic mutations in HER2-positive and triple negative normal-like feline mammary carcinoma subtypespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDeveloping diagnostic tools for feline mammary carcinomas and improving chemotherapy based on HER2 and topoisometase status
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCVT-EPI%2F3638%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F132260%2F2017/PT
oaire.citation.issue6pt_PT
oaire.citation.titleCancerspt_PT
oaire.citation.volume12pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameNascimento
person.familyNameUrbano
person.familyNameGameiro
person.familyNameFerreira
person.familyNameJesus Correia
person.familyNameFerreira
person.givenNameCatarina
person.givenNameAna Catarina
person.givenNameAndreia
person.givenNameJoão António Augusto
person.givenNameJorge Manuel
person.givenNameFernando António da Costa
person.identifier1171660
person.identifier1183692
person.identifier.ciencia-idB718-5199-AA36
person.identifier.ciencia-id2317-6BE3-E5F4
person.identifier.ciencia-idEA1C-91BA-1C8B
person.identifier.ciencia-id7311-54F2-A545
person.identifier.ciencia-idF81F-D7D4-57C5
person.identifier.orcid0000-0002-2889-4910
person.identifier.orcid0000-0003-3755-777X
person.identifier.orcid0000-0002-1602-3552
person.identifier.orcid0000-0002-1909-4540
person.identifier.orcid0000-0001-5765-576X
person.identifier.scopus-author-id57215430973
person.identifier.scopus-author-id57215434573
person.identifier.scopus-author-id7202364133
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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