Dendritic cells (DCs) stimulated with triiodothyronine (T3) enhances antitumor immunity in a murine colon cancer model

SOLER MF; ALAMINO VA; GIUSIANO L; PELLIZAS CG; MONTESINOS MM

Buenos Aires

Congreso; Biosciences Annual Meeting; 2017

Sociedad Argentina de Inmunología (SAI)

We reported that mice DCs express thyroid hormone receptor β1 and that T3 stimulates their maturation and ability to direct Th1 adaptive responses, and T cytotoxic and antitumoral effects in an in vivo model of B16-OVA melanoma. Antitumor vaccination based on the own patient DCs, loaded ex-vivo with tumor antigens, aims to reduce or eradicate tumor cells. However, protocols deserve optimi-zation since tumor cell cargo and DCs? functional state induced by maturation signals infuence their in vivo immunogenic potential. Our aim was to analyze the anti-tumor effcacy of tumor antigen-loaded DCs matured by T3 in a murine colon cancer model. MC38 cells were UV-irradiated and apoptotic and necrotic (A/N-MC38) cells were measured by AnnexinV / 7-AAD assay. Immature DCs (iDCs, control) or T3-stimulated DCs (T3-DCs) were co-incubated with A/N-MC38 cells for 18 h. Intracellular and secreted IL-12 produc-tion were assayed by fow cytometry and ELISA, respectively. MC38 cells were s.c. injected on the fank of C57BL/6 mice (day 0). Con-trol or T3-DCs co-cultured with A/N-MC38 cells were injected s.c. at days 1, 3, 5, 7 and 12. Tumor size was measured using calipers (tumor volume = L×W2/2, L = length, W = width). T3-stimulated DCs cultured with A/N-MC38 cells produced higher amount of IL-12 than iDCs (p<0.01). Mice immunized with T3-DCs plus A/N-MC38 cells showed a signifcant decrease in tumor size (day 22, p<0.05). An increased number of infltrating intratumoral CD8+ T cells in mice re-ceiving T3-DCs cultured with A/N-MC38 cells vs control was revealed (fow cytometry, p<0.05). Moreover, the immunotherapy based on T3-DCs decreased the frequency of Treg cells from splenocytes, as-sessed by a reduction of CD4+CD25+FoxP3+ cells (p<0.05). These results reinforce the adjuvant properties of T3-conditioned DCs as an alternative approach to potentiate T-cell-mediated tumor immuni-ty reported in other murine tumor model and highlight the profound implications for cancer immunotherapy