Anti-tumor immune response modulation by thyroid status influences the dissemination of a murine T cell lymphoma

STERLE H; VALLI E; PAULAZO M; COLOMBO L; BARREIRO ARCOS M; CREMASCHI G

Florianópolis

Congreso; XV Latin American Thyroid Congreso (LATS); 2013

Sociedad Latinoamericana de Tiroides

Background: we have previously shown that thyroid hormones (THs) are able to regulate the immune system, but their role in antitumor responses is not well known. Objetive: Our aim was to evaluate THs involvement in the development of a T cell lymphoma, with the focus on their effects on the immune system response. Methods: We developed murine models of hyper- and hypothyroidism in C57BL/Hep mice by oral administration of T4 or the anti-thyroid agent propylthiouracil respectively. These mice were further inoculated subcutaneously with the EL-4 lymphoma cell line to obtain solid tumors and intravenously to evaluate tumor dissemination. Results: Hyperthyroid mice showed a higher tumor growth rate and higher tumor volume than eu- and hypothyroid ones, which was related with the modulation of genes involved in the cell cycle regulation. We additionally observed that hypothyroid and hyperthyroid mice developed, respectively, a higher and lower number of metastases than controls. We found that hyperthyroid animals showed an increased number of NK and CD8+ cells accompanied with an increased NK cytotoxic activity, while hypothyroid animals showed a reduced tumour-specific T lymphocyte cytotoxic activity. Conclusions: These results suggest that thyroid status can directly modulate tumor development through the regulation of tumor growth and could regulate tumor dissemination through the modulation of the anti-tumor immune response.