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

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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 NK cells. Here, we demonstrated that, while the RMA tumor grew in syngeneic mice, DNAM-1 ligands-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 CD8α+, rather than CD8α-, dendritic cells. Cross-linking DNAM-1 induced maturation of CD8α+ dendritic cells. Antigen presentation by these stimulated dendritic cells drived Th1 cells. Moreover, the rejection of DNAM-1 ligands-transduced RMA was canceled in CD4+ T cell-depleted and MHC class II deficient mice. Taken together, these results suggest that DNAM-1 ligands stimulate innate immunity by CD8α+ dendritic cells as well as NK cells, which efficiently prime cell-mediated tumor specific immunity.