T3 improves mice colon cáncer antitumor responses stimulated by dendritic cells (DCs). Role of T3 in human DCs

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

Buenos Aires

Congreso; XVII Latin American Thyroid Congress; 2019

LatinAmerican Thyroid Society LATS

ntroduction: Vaccination with DCs loaded with tumor antigens (Ags) is a promising approach to induce specific antitumorimmunity. However, protocols of DC-based antitumor vaccines deserve optimization for in vivo efficacy. We provided evidence of acritical role for T3 controlling DC maturation and improving antitumor driven functions of DCs in a melanoma model in mice.Objectives: 1) to analyze the antitumor potential directed by T3-stimulated DCs loaded with tumor Ags in a colon cancer murinemodel; 2) to assess the effect of T3 on human DCs (hDCs) for future translation to oncotherapeutics.Methods: Colon cancer MC38 cells were UV-irradiated to induce apoptotic cells (Apo-MC38). Immature DCs (iDCs) or T3-stimulated DCs (5 nM for 18h, T3-DCs) were incubated with Apo-MC38. IL-12 production by DCs was assayed (FACS/ELISA).MC38 cells were s.c. injected to C57BL/6 mice (day 0). iDCs or T3-DCs pulsed with Apo-MC38 were s.c. injected at days 1, 3, 5, 7after tumor cell inoculation and tumor volume was measured. Lymphocyte linages in tumor-draining lymph nodes and spleen weredetermined (FACS). hDCs were pulsed with T3 (5 nM for 18h), and surface phenotype and IL-12 production were analysed byFACS. Statistics: ANOVA-SNK, p<0.05.Results: 1a) T3-DCs cultured with Apo-MC38 (T3-DCs-Ag) increased IL-12 production. 1b) Mice immunized with T3-DCs-Agshowed a decrease in tumor volume. 1c) Mice receiving T3-DCs-Ag showed an increase in proinflammatory and cytotoxiclymphocytes and a decrease in T regulatory cells in spleen and lymph nodes. 2) T3 stimulated hDC maturation and functionality.Conclusion: T3 enhances mice DCs ability to drive T-cell-mediated antitumor immunity. Furthermore, future implications forhuman immunotherapy in cancer are provided.