IFN-gamma-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, alpha-galactosylceramide.

Hayakawa Y, Takeda K, Yagita H, Smyth MJ, Van Kaer L, Okumura K, Saiki I
Blood. 2002 100 (5): 1728-33

PMID: 12176894

Alpha-galactosylceramide (alpha-GalCer), which is a specific ligand for CD1d-restricted variable-alpha14 chain (V(alpha)14) natural killer T (NKT) cells, exerts a potent antitumor effect. We recently demonstrated that interferon-gamma (IFN-gamma) secreted by both NKT cells and NK cells plays a critical role in mediating the antimetastatic effect of alpha-GalCer; however, the IFN-gamma-dependent antitumor mechanisms remain poorly defined. In the present study, we demonstrate IFN-gamma-dependent inhibition of tumor angiogenesis by alpha-GalCer. In alpha-GalCer-treated mice, subcutaneous tumor growth and tumor-induced angiogenesis were inhibited in an IFN-gamma-dependent manner. The alpha-GalCer-activated splenic or hepatic mononuclear cells inhibited murine endothelial cell proliferation in vitro, and this inhibitory effect was mediated mostly by IFN-gamma produced by NKT cells and NK cells. NK cell depletion resulted in significant but partial inhibition of tumor growth and angiogenesis in vivo. These results suggest that the IFN-gamma-mediated inhibition of tumor angiogenesis is critically involved in the effector mechanisms of antitumor effects evoked by alpha-GalCer.

MeSH Terms (10)

Animals Galactosylceramides Interferon-gamma Killer Cells, Natural Ligands Mice Mice, Inbred BALB C Mice, Inbred C57BL Neoplasms, Experimental Neovascularization, Pathologic

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