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Open AccessArticle

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

1
CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, Lisboa 1300-477, Portugal
2
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1386; https://doi.org/10.3390/cancers12061386
Received: 16 April 2020 / Revised: 25 May 2020 / Accepted: 26 May 2020 / Published: 28 May 2020
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. View Full-Text
Keywords: feline mammary carcinoma; PD-1; PD-L1; CTLA-4; TNF-α; biomarkers; immunotherapy feline mammary carcinoma; PD-1; PD-L1; CTLA-4; TNF-α; biomarkers; immunotherapy
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MDPI and ACS Style

Nascimento, C.; Urbano, A.C.; Gameiro, A.; Ferreira, J.; Correia, J.; Ferreira, F. 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. Cancers 2020, 12, 1386. https://doi.org/10.3390/cancers12061386

AMA Style

Nascimento C, Urbano AC, Gameiro A, Ferreira J, Correia J, Ferreira F. 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. Cancers. 2020; 12(6):1386. https://doi.org/10.3390/cancers12061386

Chicago/Turabian Style

Nascimento, Catarina; Urbano, Ana C.; Gameiro, Andreia; Ferreira, João; Correia, Jorge; Ferreira, Fernando. 2020. "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" Cancers 12, no. 6: 1386. https://doi.org/10.3390/cancers12061386

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