Understanding of the immunological heterogeneity of canine mammary carcinomas to provide immunophenotypic features of circulating leukocytes as clinically relevant prognostic biomarkers |
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Authors: | Alessandra Estrela-Lima Márcio Sobreira Silva Araújo João Moreira da Costa-Neto Lorena Gabriela Rocha Ribeiro Karine Araújo Damasceno Mário Jorge Melhor Heine D’Assis Olindo Assis Martins-Filho Andréa Teixeira-Carvalho Rogéria Serakides Geovanni Dantas Cassali |
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Institution: | Laboratório de Patologia Comparada, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil, Caixa Postal 486, Belo Horizonte, MG, 31270-901, Brazil. |
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Abstract: | We have evaluated the phenotypic features of peripheral blood leukocytes as putative novel biomarkers with prognostic values
to monitor canine mammary carcinomas. Female dogs were categorized into distinct groups, referred as mammary carcinoma in
benign mixed tumor-MC-BMT and mammary carcinoma-MC. Our findings demonstrate that decreased percentage of B-cells along with
increased frequency of NK-cells, CD8+T-cells, and CD8+CD5Low+T-cells beside higher T/B-cells and lower CD4+/CD8+ ratio were the hallmarks of MC-BMT. Despite the lower expression of MHCI and MHCII, the lymphocytes from MC-BMT and MC displayed
higher migration potential as suggested by enhanced frequency of CD18+ events. Although increased levels of macrophage-like cells/(CD14+CD16+) and decreased levels of MHCII expression were a common phenotypic feature in mammary carcinoma, down-regulation of MHCI
was selectively observed in MC. Decreased frequency of CD4+ T-cells with increased levels of CD8+ T-cells and lower CD4+/CD8+ T-cell ratio were relevant biomarkers of MC-BTM(−). Although decreased expression of MHCI by monocytes was observed in MC-BTM
regardless of the presence of lymph node metastasis, this phenotypic feature was restricted to MC free of metastasis. The
CD4+/CD8+ T-cells ratio lower than 1.8 was elected as a valid parameter with outstanding performance to predict survival in MC-BMT.
On the other hand, the MHCI expression by monocytes higher than 102 MFI showed good value to estimate worse outcome in MC. These results should help to improve our understanding of the immunological
heterogeneity of canine mammary carcinomas and provide tools for the determination of cut-off scores of clinically relevant
immonophenotypic prognostic biomarkers. |
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