DNAM-1

Shibuya Lab
Research Project
DNAM-1

DNAM-1 (CD226) is a member of the immunoglobulin superfamily and is constitutively expressed on the majority of NK cells, CD8+ T cells, CD4+ T cells, monocytes, and platelets. CD155 (also known as poliovirus receptor (PVR), Necl-5 or Tage4) and CD112 (also known as PRR-2 or nectin-2) are ligands for human and mouse DNAM-1. Although CD155 and CD112 are broadly distributed on epithelial and endothelial cells in many tissues, they are overexpressed on certain tumors. CD155 and CD112 expression might be induced by tumorigenesis. Interactions between DNAM-1 on NK cells and T cells and its ligands on tumor cells augment cell-mediated cytotoxicity and cytokine production in vitro. However, it remained unclear whether DNAM-1 is involved in tumor immune surveillance in vivo. To address this question, we generated DNAM-1-deficient mice. These mice showed increased tumor development and mortality after transplantation of Meth A cells that substantially expressed the DNAM-1 ligand CD155. Moreover, they developed significantly more DNAM-1 ligand-expressing fibrosarcoma and papilloma cells in response to the chemical carcinogens MCA and 7,12-dimethylbenz[a]anthracene (DMBA), respectively, than did wild-type mice. These results indicate that DNAM-1 plays an important role in immune surveillance of tumor development.