title: Antitumor Responses Stimulated by Dendritic Cells Are Improved by Triiodothyronine Binding to the Thyroid Hormone Receptor β.
abstract: 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.
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: Vanina A
authors: VA
authors: Alamino
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: Iván D
authors: ID
authors: Mascanfroni
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: María M
authors: MM
authors: Montesinos
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: Nicolás
authors: N
authors: Gigena
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: Ana C
authors: AC
authors: Donadio
authors: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET) and Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Ada G
authors: AG
authors: Blidner
authors: Hospital Materno-Neonatal Ramón Carrillo, Sanatorio Allende, Córdoba, Argentina.
authors: Sonia I
authors: SI
authors: Milotich
authors: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors: Sheue-Yann
authors: SY
authors: Cheng
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: Ana M
authors: AM
authors: Masini-Repiso
authors: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET) and Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Gabriel A
authors: GA
authors: Rabinovich
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. claudia@fcq.unc.edu.ar.
authors: Claudia G
authors: CG
authors: Pellizas
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D002470:Cell Survival; D045142:Cross-Priming; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007167:Immunotherapy; D008198:Lymph Nodes / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine