2B4(CD244)-Mediated Activation of NK Cells Reduces Metastases of B16F10 Melanoma in Mice

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-γ. 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-γ 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.