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Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12008/39751 How to cite
Title: The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer
Authors: Festari, María Florencia
da Costa, Valeria
Rodríguez-Zraquia, Santiago A.
Costa, Monique
Landeira, Mercedes
Lores, Pablo
Solari-Saquieres, Patricia
Kramer, M. Gabriela
Freire, Teresa
Type: Artículo
Keywords: Immunoregulation, Metastasis, Tn antigen, Triple negative breast cancer, Tumor growth
Descriptors: LUNG NEOPLASM, TRIPLE NEGATIVE BREAST NEOPLASMS, METABOLISM, PATHOLOGY, ANTIGENS, CELL LINE, ANTIGENOS, LINEA CELULAR, NEOPLASIAS PULMONARES, METABOLISMO, PATOLOGIA, NEOPLASIAS DE LA MAMA TRIPLE NEGATIVAS
Issue Date: 2021
Abstract: Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors.
Description: Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay -- Contacto: tfreire@fmed.edu.uy
Publisher: Oxford University Press
IN: Glycobiology, 2022, 32(5): 366–379
Citation: Festari F, da Costa V, Rodríguez-Zraquia S y otros. The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer. Glycobiology [en línea] 2022, 32(5): 366–379
ISSN: 0959-6658
License: Licencia Creative Commons Atribución (CC - By 4.0)
Appears in Collections:Publicaciones Académicas y Científicas - Facultad de Medicina

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