Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancer

Feline invasive mammary carcinomas are characterized by their high clinical aggressiveness, rare expression of hormone receptors, and pathological resemblance to human breast cancer, especially triple-negative breast cancer (negative to estrogen receptor, progesterone receptor, and epidermal growth...

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Published in:	Tumor biology Vol. 42; no. 1; p. 1010428319901052
Main Authors:	Dagher, Elie, Simbault, Laura, Abadie, Jérôme, Loussouarn, Delphine, Campone, Mario, Nguyen, Frédérique
Format:	Journal Article
Language:	English
Published:	London, England SAGE Publications 01-01-2020 Sage Publications Ltd Springer Verlag IOS Press
Subjects:	Animal models Animals Breast cancer Breast carcinoma Cancer Cancer immunotherapy Cats Cell survival Cytokeratin Disease Models, Animal Epidermal growth factor ErbB-2 protein Estrogen receptors Female Forkhead protein Gene expression Humans Immunohistochemistry Immunohistochemistry - methods Immunoregulation Immunosuppression - methods Immunotherapy Invasiveness Life Sciences Lymphocytes Lymphocytes T Mammary gland Mammary Neoplasms, Animal - metabolism Mammary Neoplasms, Animal - pathology Progesterone Prognosis Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism Retrospective Studies Surgery T-Lymphocytes, Regulatory - metabolism T-Lymphocytes, Regulatory - pathology Triple Negative Breast Neoplasms - metabolism Triple Negative Breast Neoplasms - pathology Tumor Microenvironment - physiology regulatory T cells forkhead box protein P3 feline mammary carcinoma immune tumor microenvironment Basal-like breast cancer
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Summary:	Feline invasive mammary carcinomas are characterized by their high clinical aggressiveness, rare expression of hormone receptors, and pathological resemblance to human breast cancer, especially triple-negative breast cancer (negative to estrogen receptor, progesterone receptor, and epidermal growth factor receptor type 2). Recent gene expression studies of triple-negative breast cancers have highlighted their heterogeneity and the importance of immune responses in their biology and prognostic assessment. Indeed, regulatory T cells may play a crucial role in producing an immune-suppressed microenvironment, notably in triple-negative breast cancers. Feline invasive mammary carcinomas arise spontaneously in immune-competent animals, in which we hypothesized that the immune tumor microenvironment also plays a role. The aims of this study were to determine the quantity and prognostic value of forkhead box protein P3-positive peritumoral and intratumoral regulatory T cells in feline invasive mammary carcinomas, and to identify an immune-suppressed subgroup of triple-negative basal-like feline invasive mammary carcinomas. One hundred and eighty female cats with feline invasive mammary carcinomas, treated by surgery only, with 2-year follow-up post-mastectomy, were included in this study. Forkhead box protein P3, estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor type 2, and cytokeratin 14 expression were assessed by automated immunohistochemistry. Peritumoral regulatory T cells were over 300 times more abundant than intratumoral regulatory T cells in feline invasive mammary carcinomas. Peritumoral and intratumoral regulatory T cells were associated with shorter disease-free interval and overall survival in both triple-negative (ER–, PR–, HER2–, N = 123 out of 180) and luminal (ER+ and/or PR+, N = 57) feline invasive mammary carcinomas. In feline triple-negative basal-like (CK14+) mammary carcinomas, a regulatory T-cell–enriched subgroup was associated with significantly poorer disease-free interval, overall survival, and cancer-specific survival than regulatory T-cell-poor triple-negative basal-like feline invasive mammary carcinomas. High regulatory T-cell numbers had strong and negative prognostic value in feline invasive mammary carcinomas, especially in the triple-negative basal-like subgroup, which might contain a “basal-like immune-suppressed” subtype, as described in triple-negative breast cancer. Cats with feline invasive mammary carcinomas may thus be interesting spontaneous animal models to investigate new strategies of cancer immunotherapy in an immune-suppressed tumor microenvironment.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1010-4283 1423-0380
DOI:	10.1177/1010428319901052