Antitumor immune responses generated by Triiodothyronine (T3)-stimulated Dendritic Cells (DCs) loaded with tumor specific antigens in a murine colon cancer model. Role of T3 in human DCs

SOLER MF; NEGRETTI BORGA DANA; BRAVO MIANA RC; DONADIO AC; PELLIZAS CG; MONTESINOS MM

Chicago

Congreso; 89th Anual Meeting of the American Thyroid Association; 2019

American Thryroid Association (ATA)

We reported that mice DCs, the main antigen (Ag)-presenting cells,express thyroid hormone receptor and that T3 stimulates the maturation of DCs and their ability to direct adaptive responses towards aTh1- and Th17-type profiles, as well as cytotoxic and antitumor effects. Given their potential to stimulate adaptive antitumor immuneresponses, tumor Ag?loaded DCs have come in recent years aspharmacological tools for cancer immunotherapy. However, methods of vaccine preparation deserve optimization since tumor cellcargo and DC functional state induced by maturation signals influence theirin vivo immunogenic potential. Objectives:1) to analyzethe antitumor potential directed by T3-stimulated DCs loaded withtumor Ags in a colon cancer murine model; 2) to assess the effect ofT3 on human DCs (hDCs) for future translation to oncotherapeutics.Colon cancer MC38 cells were UV-irradiated to induce apoptotic andnecrotic cells (A/N-MC38). Immature DCs (iDCs) or T3-stimulatedDCs (5nM for 18h, T3-DCs) were incubated with A/N-MC38. DC?sintracellular and secreted IL-12 production were assayed by FACSand ELISA. MC38 cells werescinjected to C57BL/6 mice (day 0).iDCs or T3-DCs pulsed with A/N-MC38 werescinjected at days 1, 3,5, 7 after tumor cell inoculation and tumor volume was measured.Lymphocyte linages in tumor-draining lymph nodes and spleen weredetermined (FACS). hDCs were pulsed with T3 (5nM for 18h), andsurface phenotype and IL-12 production were analysed by FACS.Statistics:ANOVA-SNK, p<0.05.1a)T3-DCs cultured with A/NMC38 cells produced higher amount of IL-12 than iDCs. 1b) Tumorbearing mice immunized with T3-DCs loaded with tumor-Agsshowed an inhibition in tumor growth. 1c) Mice receiving T3-DCsAg showed an increase in proinflammatory and Ags specific cytotoxic lymphocytes, as well as a decrease in T regulatory cells inspleen and lymph nodes. 2)T3 induces phenotypic and functional activation of hDCs, with an increase in CD86 expression and IL-12production. These results suggest that T3 endows mice DCs withenhanced ability to potentiate a specific T-cell-mediated antitumorimmunity. Furthermore, our findings in hDCs support promisingadvances in the translation process to human oncotherapy.