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Thyroid status regulates the tumor microenvironment delineating breast cancer fate.
- Source :
-
Endocrine-Related Cancer . Jul2021, Vol. 28 Issue 7, p403-418. 16p. - Publication Year :
- 2021
-
Abstract
- 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. We evaluated the effect of thyroid status on breast cancer growth a nd 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 tumo r 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 e xhibited 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 c ancer. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13510088
- Volume :
- 28
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Endocrine-Related Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 151036125
- Full Text :
- https://doi.org/10.1530/ERC-20-0277