The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer

Festari, María Florencia - da Costa, Valeria - Rodríguez-Zraquia, Santiago A. - Costa, Monique - Landeira, Mercedes - Lores, Pablo - Solari-Saquieres, Patricia - Kramer, M. Gabriela - Freire, Teresa

Resumen:

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.


Detalles Bibliográficos
2021
Immunoregulation
Metastasis
Tn antigen
Triple negative breast cancer
Tumor growth
LUNG NEOPLASM
TRIPLE NEGATIVE BREAST NEOPLASMS
METABOLISM
PATHOLOGY
ANTIGENS
CELL LINE
ANTIGENOS
LINEA CELULAR
NEOPLASIAS PULMONARES
METABOLISMO
PATOLOGIA
NEOPLASIAS DE LA MAMA TRIPLE NEGATIVAS
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/39751
https://doi.org/10.1093/glycob/cwab123
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)
Resumen:
Sumario:Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay -- Contacto: tfreire@fmed.edu.uy