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; Reunión Conjunta de Sociedades de Biociencias; 2017

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 optimization since tumor cell cargo and DCs? functional state induced by maturation signals influence their in vivo immunogenic potential. Our aim was to analyze the anti-tumor efficacy 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 production were assayed by flow cytometry and ELISA, respectively. MC38 cells were s.c. injected on the flank of C57BL/6 mice (day 0). Control 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 significant decrease in tumor size (day 22, p<0.05). An increased number of infiltrating intratumoral CD8+ T cells in mice receiving T3-DCs cultured with A/N-MC38 cells vs control was revealed (flow cytometry, p<0.05). Moreover, the immunotherapy based on T3-DCs decreased the frequency of Treg cells from splenocytes, assessed 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 immunity reported in other murine tumor model and highlight the profound implications for cancer immunotherapy.