Clinical relevance of the CTLA-4 protein in cats with mammary carcinoma

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Clinical relevance of the CTLA-4 protein in cats with mammary carcinoma

Monday, 13.04.2020

Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) serves an important role in breast cancer progression, which has led to the development of novel immunotherapies aimed at blocking tumor immune evasion. Although feline mammary carcinoma is increasingly recognized as a valuable cancer model, no studies on CTLA-4 function had been conducted in this species. The serum CTLA-4, TNF-α and IL-6 levels of 57 female cats with mammary carcinoma were determined by ELISA, and immunohistochemistry was performed to evaluate CTLA-4 and FoxP3 expression in tumor cells and interstitial lymphocytes. The results obtained show that serum CTLA-4 levels are increased in cats with mammary carcinoma (P = 0.022), showing an association with a number of clinicopathological features: smaller tumor size, P < 0.001; absence of tumor necrosis, P < 0.001; non-basal status, P < 0.02 and HER-2-positive status. Additionally, a strong positive correlation was found between serum CTLA-4 levels and serum TNF-α (R = 0.88, P < 0.001) and IL-6 levels (R = 0.72, P < 0.001). Concerning the CTLA-4 and FoxP3 expression, although detected in both interstitial lymphocytes and tumor cells, a positive association was found only between interstitial CTLA-4 and FoxP3 expressions (R = 0.387, P = 0.01), which is negatively associated with the serum CTLA-4 levels (P = 0.03). These findings provide a preliminary step in the characterization of immune profiles in feline mammary carcinoma, uncovering a molecular rationale for targeted therapy with CTLA-4 pathway inhibitors. Finally, by strengthening the hypothesis of an immunomodulatory role for this regulator, we further validate the utility of spontaneous feline mammary carcinoma as a model for human breast cancer.


Authors and Affiliations:

Ana Catarina Urbano1, Catarina Nascimento1, Maria Soares2, Jorge Correia1, Fernando Ferreira1
1CIISA - Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, Lisboa, 1300-477, Portugal
2Research Center for Biosciences and Health Technologies (CBiOS), Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias (ULHT), Lisboa, 1749-024, Portugal

Journal: Scientific Reports