Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor

The poliovirus receptor CD155 and its family member CD112 (nectin-2) are the ligands for the activating cell-surface receptor DNAM-1 on CD8(+) T cells and natural killer (NK) cells. Here, we demonstrate that, whereas the RMA tumor grew in syngeneic mice, DNAM-1 ligand-transduced RMA was rejected, in which CD8(+) T cells and NK cells played an essential role. Importantly, CD8(+) memory cytotoxic T cells to parental RMA were generated in these mice. We found that DNAM-1 was also expressed on CD8 alpha(+), rather than CD8 alpha(-), dendritic cells (DCs). Cross-linking DNAM-1 induced maturation of CD8 alpha(+) DCs. Antigen presentation by these stimulated DCs drove Th1 cells. Moreover, the rejection of DNAM-1 ligand-transduced RMA was canceled in CD4(+) T-cell-depleted and major histocompatibility complex class II-deficient mice. Taken together, these results suggest that DNAM-1 ligands stimulate innate immunity by CD8 alpha(+) DCs as well as NK cells, which efficiently prime cell-mediated tumor-specific immunity. (Blood. 2006;107: 1491-1496) (c) 2006 by The American society of Hematology.