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Accelerated tumor growth in mice deficient in DNAM-1 receptor

Akiko Iguchi-Manaka1, Hirayasu Kai, Yumi Yamashita

  • 1Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.

The Journal of Experimental Medicine
|November 26, 2008
PubMed

Insights

DNAM-1 is crucial for immune surveillance against tumors. Mice lacking DNAM-1 showed reduced T and NK cell activity, leading to increased tumor development and mortality.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Immunology

Background:

  • DNAM-1 (DNAX accessory molecule-1) is implicated in T cell and NK cell recognition of tumor cells.
  • Its role in in vivo tumor immune surveillance remains unclear.

Purpose of the Study:

  • To investigate the role of DNAM-1 in tumor immune surveillance in vivo.
  • To determine if DNAM-1 deficiency affects tumor development and susceptibility to carcinogens.

Main Methods:

  • Utilized DNAM-1-deficient mice and wild-type (WT) controls.
  • Assessed cytotoxic activity of T cells and NK cells against DNAM-1 ligand-expressing tumors in vitro.
  • Evaluated tumor development and mortality after Meth A fibrosarcoma cell transplantation.
  • Examined fibrosarcoma and papilloma development in response to chemical carcinogens (MCA and DMBA).

Main Results:

  • DNAM-1-deficient CTL and NK cells exhibited reduced cytotoxic activity against tumors expressing DNAM-1 ligands in vitro.
  • DNAM-1-deficient mice showed increased tumor development and mortality upon Meth A cell transplantation.
  • These mice also developed more DNAM-1 ligand-expressing fibrosarcoma and papilloma cells after exposure to MCA and DMBA, respectively.

Conclusions:

  • DNAM-1 plays a significant role in the in vivo immune surveillance of tumor development.
  • DNAM-1 is essential for effective anti-tumor responses mediated by T cells and NK cells.

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