Beta‐Glucosylceramide Administration (i.p.) Activates Natural Killer T cells In Vivo and Prevents Tumor Metastasis in Mice

Abstract

Natural killer (NK) T cells are well known to play important roles in both tumor rejection and the defense against infectious. Therefore, the antitumor potential of NKT cell-activating antigens have been the focus for the development of NKT cell-based immunotherapies. Up to now, several studies have revealed that the administrations of glycolipids (e.g. α-galactosylceramide) can successfully treat certain metastatic tumors. However, liver injuries appeared upon the application of these antigens. We previously examined the potential of using β-glucosylceramide (β-GlcCer) to inhibit tumor metastasis to the liver. The aim of this study was to determine the antimetastatic effects of β-GlcCer and its impact on the activation of NKT cells. Intraperitoneal administration of β-GlcCer enhanced the production of interferon-γ from hepatic lymphocytes containing NKT cells, and increased the cytotoxicity of hepatic lymphocytes against tumor cells. Moreover, β-GlcCer administration suppressed the hepatic metastasis of tumors in wild type (WT) mice, but not in CD1d (-/-) or Jα18 (-/-) mice. The drawback associated with the other glycolipids in liver injury was not noted in WT mice treated with the continuous daily administration of β-GlcCer for 2 weeks. The present study demonstrated that β-GlcCer treatment activates invariant NKT cells, thus resulting in the inhibition of tumor metastasis.