Antitumor responses stimulated by dendritic cells are improved by triiodothyronine binding to the thyroid hormone receptor beta.

ALAMINO VA; MASCANFRONI ID; MONTESINOS MM; GIGENA N; DONADIO AC; BLIDNER AG; MILOTICH SI; CHENG SY; MASINI-REPISO AM; RABINOVICH GA; PELLIZAS CG

CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

Año: 2015 vol. 75 p. 1265 - 1265

0008-5472

idirectional 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) b mutant mouse (TRbPV) to establish the relevance of the T3-TRb system in vivo. In this model, TRb signaling endowed DCs with the ability to stimulate antigen-specific cytotoxic T-cell responses during tumor development. T3 binding to TRb 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 IFNg-producing CD8þ T cells.