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

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

CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

Lugar: Philadelphia; Año: 2015 vol. 75 p. 1265 - 1274

0008-5472

Bi-directional crosstalk 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 DC 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 DC to cross-present antigens and to stimulate cytotoxic T cell responses. In a B16-OVA mouse model of melanoma, vaccination with T3-stimulated DC inhibited tumor growth and prolonged host survival, in part by promoting the generation of IFN-γ-producing CD8+ T cells. Overall, our results establish an adjuvant effect of T3-TRβ signaling in DC, suggesting an immediately translatable method to empower DC vaccination approaches for cancer immunotherapy.