Accelerated tumor growth in mice deficient in DNAM-1 receptor

• Published in: Journal of experimental medicine Vol. 205; no. 13; pp. 2959 - 2964
• Main Authors: 甲斐 平康, 田原 聡子, 本多 伸一郎, 渋谷 和子, 渋谷 彰, Iguchi-Manaka Akiko, Kai Hirayasu, Yamashita Yumi, Shibata Kai, Tahara-Hanaoka Satoko, Honda Shin-ichiro, Yasui Teruhito, Kikutani Hitoshi, Shibuya Kazuko, Shibuya Akira
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 22.12.2008
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - pharmacology; Animals; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - immunology; Brief Definitive Reports; 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
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20081611

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. application/pdf