Accelerated tumor growth in mice deficient in DNAM-1 receptor

J Exp Med. 2008 Dec 22;205(13):2959-64. doi: 10.1084/jem.20081611. Epub 2008 Nov 24.


Since the identification of ligands for human and mouse DNAM-1, emerging evidence has suggested that DNAM-1 plays an important role in the T cell- and natural killer (NK) cell-mediated recognition and lysis of tumor cells. However, it remains undetermined whether DNAM-1 is involved in tumor immune surveillance in vivo. We addressed this question by using DNAM-1-deficient mice. DNAM-1-deficient cytotoxic T lymphocyte (CTL) and NK cells showed significantly less cytotoxic activity against DNAM-1 ligand-expressing tumors in vitro than wild-type (WT) cells. The methylcholanthrene (MCA)-induced fibrosarcoma cell line Meth A expressed the DNAM-1 ligand CD155, and DNAM-1-deficient mice showed increased tumor development and mortality after transplantation of Meth A cells. Moreover, the DNAM-1-deficient mice 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 WT mice. These results indicate that DNAM-1 plays an important role in immune surveillance of tumor development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / pharmacology
  • Animals
  • Antigens, Differentiation, T-Lymphocyte* / genetics
  • Antigens, Differentiation, T-Lymphocyte* / immunology
  • Carcinogens / pharmacology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / immunology
  • Fibrosarcoma / immunology
  • Fibrosarcoma / pathology
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Male
  • Methylcholanthrene / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neoplasm Transplantation
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Papilloma / immunology
  • Papilloma / pathology
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • Carcinogens
  • Methylcholanthrene
  • 9,10-Dimethyl-1,2-benzanthracene