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

NEGRETTI, DM; PELLIZAS, CG; BRAVO MIANA, R; MONTESINOS, MM; SOLER, MF; DONADIO, AC

Buenos Aires

Congreso; XVII Latin American Thyroid Congress; 2019

Latin American Thyroid Society

Introduction: Vaccination with DCs loaded with tumor antigens (Ags) is a promising approach to induce specific antitumor immunity.However, protocols of DC-based antitumor vaccines deserve optimization for in vivo efficacy. We provided evidence of a critical rolefor 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 murine model; 2) toassess the effect of T3 on human DCs (hDCs) for future translation to oncotherapeutics. Methods: Colon cancer MC38 cells wereUV-irradiated to induce apoptotic cells (Apo-MC38). Immature DCs (iDCs) or T3- stimulated DCs (5 nM for 18h, T3-DCs) wereincubated 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, 7 after tumor cell inoculation and tumor volume wasmeasured. Lymphocyte linages in tumor-draining lymph nodes and spleen were determined (FACS). hDCs were pulsed with T3 (5 nMfor 18h), and surface phenotype and IL-12 production were analysed by FACS. 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-Ag showed a decreasein tumor volume. 1c) Mice receiving T3-DCs-Ag showed an increase in proinflammatory and cytotoxic lymphocytes and a decreasein T regulatory cells in spleen and lymph nodes. 2) T3 stimulated hDC maturation and functionality. Conclusion: T3 enhances miceDCs ability to drive T-cell-mediated antitumor immunity. Furthermore, future implications for human immunotherapy in cancer areprovided. Conflict of interest: None declared.