info:eu-repo/semantics/article
Antitumor responses stimulated by dendritic cells are improved by triiodothyronine binding to the thyroid hormone receptor β
Fecha
2015-04Registro en:
Alamino, Vanina Alejandra; Mascanfroni, Ivan Darío; Montesinos, Maria del Mar; Gigena, Nicolás; Donadio, Ana Carolina; et al.; Antitumor responses stimulated by dendritic cells are improved by triiodothyronine binding to the thyroid hormone receptor β; American Association For Cancer Research; Cancer Research; 175; 7; 4-2015; 1265-1274
0008-5472
Autor
Alamino, Vanina Alejandra
Mascanfroni, Ivan Darío
Montesinos, Maria del Mar
Gigena, Nicolás
Donadio, Ana Carolina
Blidner, Ada Gabriela
Milotich, Sonia I.
Cheng, Sheue Yann
Masini Repiso, Ana M.
Rabinovich, Gabriel Adrian
Pellizas, Claudia Gabriela
Resumen
Bidirectional cross-talk between the neuroendocrine and immune systems orchestrates immune responses in both physiologic and pathologic settings. In this study, we provide in vivo evidence of a critical role for the thyroid hormone triiodothyronine (T3) in controlling the maturation and antitumor functions of dendritic cells (DC). We used a thyroid hormone receptor (TR) β mutant mouse (TRβPV) to establish the relevance of the T3-TRβ system in vivo. In this model, TRβ signaling endowed DCs with the ability to stimulate antigen-specific cytotoxic T-cell responses during tumor development. T3 binding to TRβ increased DC viability and augmented DC migration to lymph nodes. Moreover, T3 stimulated the ability of DCs to cross-present antigens and to stimulate cytotoxic T-cell responses. In a B16-OVA mouse model of melanoma, vaccination with T3-stimulated DCs inhibited tumor growth and prolonged host survival, in part by promoting the generation of IFNγ-producing CD8(+) T cells. Overall, our results establish an adjuvant effect of T3-TRβ signaling in DCs, suggesting an immediately translatable method to empower DC vaccination approaches for cancer immunotherapy.