The thyroid status modulates the tumor microenvironment and the antitumor immune response in breast cancer.

STERLE HA ; HILDEBRANDT X; GUTIERREZ L; PAULAZO MA; CAYROL MF; DIAZ FLAQUE MARIA; ROSEMBLIT C; BOLONTRADE MF; CREMASCHI GA,

Congreso; XVII Latin American Thyroid Society Congress.; 2019

Latin American Thyroid Society

Introduction: Several findings suggest that the patient?s hormonal context plays a crucial role in determining the outcome of cancer. However, very little is known about the nature of thyroid hormone action on tumor growth. Objectives: To evaluate the effect of thyroid status on triple negative breast cancer (TNBC) development. Methods: Balb/c mice were orthotopically inoculated with 4T1 cells after the treatment with thyroxine (12 mg/l) for 30 days or propylthiouracil (500 mg/l) for 15 days in the drinking water to obtain hyperthyroid (hyper) or hypothyroid (hypo) mice, respectively. Results: Hyper mice showed increased tumor growth rate compared to controls (p < 0.05). Hypo tumor volumes were decreased (p < 0.05), but developed a greater number of lung metastases (p < 0.05). Conditioned medium from hyper tumors induced a reduced migration of murine MSC in vitro (p < 0.05). Likewise, hyper tumors and lungs showed a decreased presence of MSC (p < 0.05) when MSC were inoculated in the tail vein of tumor-bearing mice. Also, increased secretion of MCP-1 was detected in hypo tumors (p < 0.05), while decreased production of IFNγ and increased IL-10 were detected in tumors from hyper mice (p < 0.05). Hypo tumors also showed increased levels of infiltrating immune cells and of activated CD8+ T lymphocytes (p < 0.05). However, the infiltration of immune cells was decreased in tumors from hyper mice (p < 0.05), but they showed increased frequencies of splenic activated T lymphocytes (p < 0.05) and NK cells (p < 0.05) but reduced percentages of CD11b+Gr1+ cells (p < 0.05). Conclusion: Our results suggest that the thyroid status modulates the migration of MSC to the 4T1 tumors and the antitumor immune response, thus regulating tumor growth and metastasis formation. Conflict of interest: None declared.