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

Bibliographic Details
Main Author: Nascimento, Catarina
Publication Date: 2020
Other Authors: Urbano, Ana Catarina, Gameiro, Andreia, Ferreira, João, Correia, Jorge Manuel de Jesus, Ferreira, Fernando
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/50909
Summary: © 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/).
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spelling Serum PD-1/PD-L1 levels, tumor expression and PD-L1 somatic mutations in HER2-positive and triple negative normal-like feline mammary carcinoma subtypesCTLA-4PD-1PD-L1TNF-αBiomarkersFeline mammary carcinomaImmunotherapy© 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/).Tumor 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.This 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).MDPIRepositório da Universidade de LisboaNascimento, CatarinaUrbano, Ana CatarinaGameiro, AndreiaFerreira, JoãoCorreia, Jorge Manuel de JesusFerreira, Fernando2022-01-21T12:17:21Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50909engCancers (Basel). 2020 May 28;12(6):1386. PMID: 32481540; PMCID: PMC735256110.3390/cancers120613862072-6694info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:40:26Zoai:repositorio.ulisboa.pt:10451/50909Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:21:09.898544Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv 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
title 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
spellingShingle 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
Nascimento, Catarina
CTLA-4
PD-1
PD-L1
TNF-α
Biomarkers
Feline mammary carcinoma
Immunotherapy
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
author Nascimento, Catarina
author_facet Nascimento, Catarina
Urbano, Ana Catarina
Gameiro, Andreia
Ferreira, João
Correia, Jorge Manuel de Jesus
Ferreira, Fernando
author_role author
author2 Urbano, Ana Catarina
Gameiro, Andreia
Ferreira, João
Correia, Jorge Manuel de Jesus
Ferreira, Fernando
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Nascimento, Catarina
Urbano, Ana Catarina
Gameiro, Andreia
Ferreira, João
Correia, Jorge Manuel de Jesus
Ferreira, Fernando
dc.subject.por.fl_str_mv CTLA-4
PD-1
PD-L1
TNF-α
Biomarkers
Feline mammary carcinoma
Immunotherapy
topic CTLA-4
PD-1
PD-L1
TNF-α
Biomarkers
Feline mammary carcinoma
Immunotherapy
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/).
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
2022-01-21T12:17:21Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/50909
url http://hdl.handle.net/10451/50909
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Cancers (Basel). 2020 May 28;12(6):1386. PMID: 32481540; PMCID: PMC7352561
10.3390/cancers12061386
2072-6694
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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