Thyroid status regulates the tumor microenvironment delineating breast cancer fate

STERLE, HELENA A.; HILDEBRANDT, XIMENA; VALENZUELA ALVAREZ, MATIAS; PAULAZO, MARÍA ALEJANDRA; GUTIERREZ, LUCIANA M.; KLECHA, ALICIA; CAYROL, MARIA FLORENCIA; DÍAZ FLAQUE, MARIA CELESTE; ROSEMBLIT, CINTHIA; BARREIRO ARCOS, MARIA LAURA; COLOMBO, LUCAS; BOLONTRADE, MARCELA F.; MEDINA, VANINA ; CREMASCHI, GRACIELA A.

ENDOCRINE - RELATED CANCER

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2021 vol. 28 p. 403 - 418

1351-0088

The patient?s hormonal context plays a crucial role in the outc ome of cancer. However,the association between thyroid disease and breast cancer risk remains unclear. Weevaluated the effect of thyroid status on breast cancer growth a nd dissemination in animmunocompetent mouse model. For this, hyperthyroid and hypothyroid Balb/c micewere orthotopically inoculated with triple-negative breast cancer 4T1 cells. Tumors fromhyperthyroid mice showed an increased growth rate and an immunosuppressive tumormicroenvironment, characterized by increased IL-10 levels and decreased percentageof activated cytotoxic T cells. On the other hand, delayed tumo r growth in hypothyroidanimals was associated with increased tumor infiltration of activated CD8+ cells and ahigh IFNγ/IL-10 ratio. Paradoxically, hypothyroid mice developed a higher number oflung metastasis than hyperthyroid animals. This was related to an increased secretionof tumor CCL2 and an immunosuppressive systemic environment, with increasedproportion of regulatory T cells and IL-10 levels in spleens. A lower number of lungmetastasis in hyperthyroid mice was related to the reduced presence of mesenchymalstem cells in tumors and metastatic sites. These animals also e xhibited decreasedpercentages of regulatory T lymphocytes and myeloid-derived suppressor cells in spleensbut increased activated CD8+ cells and the IFNγ/IL-10 ratio. Therefore, thyroid hormonesmodulate the cellular and cytokine content of the breast tumor microenvironment. Abetter understanding of the mechanisms involved in these effects could be a startingpoint for the discovery of new therapeutic targets for breast c ancer.