THE THYROID STATUS MODULATES THE TUMOR MICROENVIRONMENT AND THE ANTITUMOR IMMUNE RESPONSE IN BREAST CANCER

STERLE, H.A.; HILDEBRANDT, XIMENA; GUTIERREZ L; PAULAZO, M.A.; CAYROL, F.; DÍAZ FLAQUÉ, M. CELESTE; ROSEMBLIT, CINTHIA; BOLONTRADE, M; CREMASCHI, G.A.

Congreso; XVII Latin American Thyroid Society Congress.; 2019

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 ofthyroid status on triple negative breast cancer (TNBC) development. Methods: Balb/c mice were orthotopically inoculated with4T1 cells after the treatment with thyroxine (12 mg/l) for 30 days or propylthiouracil (500 mg/l) for 15 days in the drinking waterto obtain hyperthyroid (hyper) or hypothyroid (hypo) mice, respectively. Results: Hyper mice showed increased tumor growth ratecompared 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-bearingmice. Also, increased secretion of MCP-1 was detected in hypo tumors (p < 0.05), while decreased production of IFNγ and increasedIL-10 were detected in tumors from hyper mice (p < 0.05). Hypo tumors also showed increased levels of infiltrating immune cellsand 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 reducedpercentages of CD11b+Gr1+ cells (p < 0.05). Conclusion: Our results suggest that the thyroid status modulates the migration ofMSC to the 4T1 tumors and the antitumor immune response, thus regulating tumor growth and metastasis formation. Conflict ofinterest: None declared.