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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| Format: | Article |
| Language: | English |
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SAGE Publishing
2020-01-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428319901052 |
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| author | Elie Dagher Laura Simbault Jérôme Abadie Delphine Loussouarn Mario Campone Frédérique Nguyen |
| author_facet | Elie Dagher Laura Simbault Jérôme Abadie Delphine Loussouarn Mario Campone Frédérique Nguyen |
| author_sort | Elie Dagher |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-152cdd984dd447bcb2430308c118ecfb |
| institution | DOAJ |
| issn | 1423-0380 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-152cdd984dd447bcb2430308c118ecfb2025-08-20T03:15:16ZengSAGE PublishingTumor Biology1423-03802020-01-014210.1177/1010428319901052Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancerElie Dagher0Laura Simbault1Jérôme Abadie2Delphine Loussouarn3Mario Campone4Frédérique Nguyen5AMaROC, Oniris (Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering), Nantes, FranceAMaROC, Oniris (Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering), Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, Nantes, FranceAnatomie Pathologique, Hôtel-Dieu, CHU de Nantes, Nantes, FranceIntegrated Center for Oncology, ICO, Nantes, FranceIntegrated Center for Oncology, ICO, Nantes, FranceFeline 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.https://doi.org/10.1177/1010428319901052 |
| spellingShingle | Elie Dagher Laura Simbault Jérôme Abadie Delphine Loussouarn Mario Campone Frédérique Nguyen Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancer Tumor Biology |
| title | Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancer |
| title_full | Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancer |
| title_fullStr | Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancer |
| title_full_unstemmed | Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancer |
| title_short | Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancer |
| title_sort | identification of an immune suppressed subtype of feline triple negative basal like invasive mammary carcinomas spontaneous models of breast cancer |
| url | https://doi.org/10.1177/1010428319901052 |
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