2B4(CD244)-mediated activation of NK cells reduces metastases of B16F10 melanoma in mice

Anticancer Res. Sep-Oct 2003;23(5A):3651-5.

Abstract

Background: Natural killer (NK) cells are a third population of lymphocytes that can kill certain tumor cells. This killing is regulated by signals received through activating and inhibitory receptors. 2B4 (CD244), a member of the CD2 subset of Immunoglobulin superfamily, was identified as an activating receptor on NK cells. Interaction of 2B4 with its ligand CD48 or anti-2B4 mAb stimulates NK cell cytolytic function as well as production of INF-gamma.

Materials and methods: A murine tumor model was used to study the in vivo role of 2B4. 2B4 and CD48 were activated in vivo by injecting anti-2B4 and anti-CD48 monoclonal antibodies.

Results: Activation of 2B4 or CD48 resulted in a five-fold reduction in tumor metastasis. IFN-gamma knockout mice had a two-fold increase in metastasis as compared to wild-type after 2B4 activation.

Conclusion: Activation of 2B4 and CD48 reduces metastasis of B16F10 melanoma cells and this anti-tumor effect involves both cytolytic function and cytokine production.

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • CD28 Antigens / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / immunology
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / secondary
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Immunologic / immunology*
  • Signaling Lymphocytic Activation Molecule Family

Substances

  • Antigens, CD
  • CD28 Antigens
  • Cd244a protein, mouse
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Signaling Lymphocytic Activation Molecule Family
  • Interferon-gamma