FP34-6 DENDRITIC CELLS (DC) PULSED WITH THYROID HORMONE IN THE PRESENCE OF TUMOR ANTIGENS INDUCE A POTENT ANTITUMOR RESPONSE: ROLE OF TRIIODOTHYRONINE AS ADJUVANT IN DC-BASED CANCER VACCINES

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP34-Molecular Mechanisms in Thyroid Hormone Action & Cancer
Basic/Translational
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:10 AM
Room 103 (Moscone Center)

Poster Board MON-418
Vanina Alejandra Alamino*1, Nicolás Gigena1, María del Mar Montesinos1, Ana Carolina Donadio1, Sonia Ivana Milotich2, Ana María Masini-Repiso1, Gabriel Adrián Rabinovich3 and Claudia Gabriela Pellizas1
1Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET). Facultad de Ciencias Químicas. Universidad Nacional de Córdoba, Argentina, 2Hospital Materno-Neonatal Ramón Carrillo. Sanatorio Allende, Córdoba, Argentina, 3Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina
We demonstrated that mice dendritic cells (DC), the main antigen (Ag)-presenting cells, express thyroid hormone receptor (TR) β1 and that physiological levels of triiodothyronine (T3) stimulate the maturation of DC and IL-12 production. Furthermore, T3-stimulated DC increased the T cell allostimulatory capacity directing a T1-type response (1) involving PI3K-independent, Akt and NFkB activation signals (2). Moreover, T3 increased DC ability to stimulate a cytotoxic Ag-specific response in vivo and an Ag cross-presentation in vitro (3). Recently, there has been a growing interest in the application of cancer therapies based on the immunization of patients with their own DC loaded with tumor-associated Ag ex vivo as an alternative to radiotherapy and chemotherapy for malignant tumors treatment (4). However, the clinical success of DC-based immunotherapy is limited needing optimization. Considering our previous findings, we hypothesized that T3 could be a powerful adjuvant in DC-based antitumor vaccination. Objectives: 1) To evaluate apoptosis in T3-treated DC; 2) To analyze the migratory capacity of T3-stimulated DC; 3) To assess the capacity of T3-matured DC in the presence of tumor Ag to stimulate an anti-tumor immune response in vivo. Methods: Mice bone marrow derived DC were pulsed with T3 (5nM) for 18 h. Apoptosis and DC migratory ability were analyzed by standard methodologies. For mice antitumor vaccination, B16-OVA melanoma model was used and the immunotherapy consisted of four immunizations with T3-pulsed DC in the presence of OVA at 1, 3, 5 and 8 days after tumor cell inoculation. Tumors were measured with vernier calipers and animal survival was defined as the time in days between tumor cell inoculation and the day of sacrifice (tumor diameter: 2cm). P<0.05 was considered statistically significant (ANOVA, Student-Neuman-Keuls, Gehan-Bislow-Wilcoxon). Results: 1) T3 reduced DC apoptosis, 2) T3 induced DC migration to lymph nodes, 3) T3-stimulated DC-based immunotherapy was able to reduce the incidence of tumor establishment and tumor growth in affected mice, prolonging their survival. These registered antitumor effects were mediated, at least in part, by CD8+ T cells (induced by the ability of T3 to generate a Th1 profile) capable of secreting large amounts of IFN-γ. Conclusions: Our results strongly suggest significant adjuvant properties of T3 in DC-based antitumor vaccination with profound implications in cancer immunotherapy.

(1) Mascanfroni ID et al.,  FASEB J 2008; 22:1032.  (2) Mascanfroni ID et al., J Biol Chem 2010; 285:9569.  (3) Alamino VA et al., RAEM 2010; 47:90. (4) Palucka K and Banchereau J.,  Nat Rev 2012; 12: 265.

Nothing to Disclose: VAA, NG, MDMM, ACD, SIM, AMM, GAR, CGP

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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