DNAM-1 promotes inflammation-driven tumor development via enhancing IFN-gamma production

DNAM-1 is an activating immunoreceptor on T cells and natural killer (NK) cells. Expression levels of its ligands, CD155 and CD112, are up-regulated on tumor cells. The interaction of DNAM-1 on CD8(+) T cells and NK cells with the ligands on tumor cells plays an important role in tumor immunity. We previously reported that mice deficient in DNAM-1 showed accelerated growth of tumors induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Contrary to those results, we show here that tumor development induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) together with DMBA was suppressed in DNAM-1-deficient mice. In this model, DNAM-1 enhanced IFN-gamma secretion from conventional CD4(+) T cells to promote inflammation-related tumor development. These findings suggest that, under inflammatory conditions, DNAM-1 contributes to tumor development via conventional CD4(+) T cells. DNAM-1-induced IFN-gamma from CD4(+) T cells can promote tumorigenesis