Monocyte-derived dendritic cells that capture dead tumor cells secrete IL-12 and TNF-? through IL-12/TNF-?/NF-?B autocrine loop

This study focused on the question of how monocyte-derived dendritic cells (Mo-DCs) that capture dead tumor cells (Mo-DCs-Tum) secrete interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α). Mo-DCs-Tum showed higher secretions of IL-12 and TNF-α than were shown by Mo-DCs. Enhanced nuclear factor-kappa B (NF-κB) activation was also induced in Mo-DCs-Tum within 6 h. The NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), suppressed both IL-12 and TNF-α secretions from Mo-DCs-Tum. Administration of recombinant TNF-α or IL-12 enhanced IL-12 or TNF-α secretion respectively in Mo-DCs-Tum. Addition of anti-TNF-α or anti-IL-12 neutralizing antibody decreased NF-κB activation and IL-12 or TNF-α secretion in Mo-DCs-Tum. These results suggest that TNF-α or IL-12 secretion induces NF-κB activation, and it stimulates further TNF-α and IL-12 secretions, i.e., an IL-12/TNF-α/NF-κB autocrine loop, in Mo-DCs-Tum. Thus, Mo-DCs-Tum secrete a large amount of IL-12 and TNF-α through accelerated NF-κB activation induced by the IL-12/TNF-α/NF-κB autocrine loop.