Artículo
Thyroid status regulates the tumor microenvironment delineating breast cancer fate
Registro en:
1351-0088
1479-6821 (online)
10.1530/ERC-20-0277
Autor
Sterle, Helena Andrea
Hildebrandt, Ximena
Valenzuela Álvarez, Matías
Paulazo, Maria Alejandra
Gutierrez, Luciana Mariel
Klecha, Alicia Juana
Cayrol, María Florencia
Díaz Flaqué, María Celeste
Rosemblit, Cinthia
Barreiro Arcos, María Laura
Colombo, Lucas Luis
Bolontrade, Marcela Fabiana
Medina, Vanina Araceli
Cremaschi, Graciela A.
Institución
Resumen
Abstract:
The patient’s hormonal context plays a crucial role in the outcome of cancer. However,
the association between thyroid disease and breast cancer risk remains unclear. We
evaluated the effect of thyroid status on breast cancer growth and dissemination in an
immunocompetent mouse model. For this, hyperthyroid and hypothyroid Balb/c mice
were orthotopically inoculated with triple-negative breast cancer 4T1 cells. Tumors from
hyperthyroid mice showed an increased growth rate and an immunosuppressive tumor
microenvironment, characterized by increased IL-10 levels and decreased percentage
of activated cytotoxic T cells. On the other hand, delayed tumor growth in hypothyroid
animals was associated with increased tumor infiltration of activated CD8+ cells and a
high IFNγ/IL-10 ratio. Paradoxically, hypothyroid mice developed a higher number of
lung metastasis than hyperthyroid animals. This was related to an increased secretion
of tumor CCL2 and an immunosuppressive systemic environment, with increased
proportion of regulatory T cells and IL-10 levels in spleens. A lower number of lung
metastasis in hyperthyroid mice was related to the reduced presence of mesenchymal
stem cells in tumors and metastatic sites. These animals also exhibited decreased
percentages of regulatory T lymphocytes and myeloid-derived suppressor cells in spleens
but increased activated CD8+ cells and the IFNγ/IL-10 ratio. Therefore, thyroid hormones
modulate the cellular and cytokine content of the breast tumor microenvironment. A
better understanding of the mechanisms involved in these effects could be a starting
point for the discovery of new therapeutic targets for breast cancer.