Inafuku Masashi, Li Changchun, Kanda Yasuhiro, Kawamura Toshihiko, Takeda Kazuyoshi, Oku Hirosuke, Watanabe Hisami
Department of Health Sciences, Trans-disciplinary Research Organization for Subtropics and Island Studies, University of the Ryukyus, Senbaru 1, Nishihara, Okinawa 903-0213, Japan.
Lipids. 2012 Jun;47(6):581-91. doi: 10.1007/s11745-012-3666-1. Epub 2012 Mar 20.
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.
自然杀伤（NK）T细胞在肿瘤排斥和抗感染防御中均发挥重要作用，这已广为人知。因此，NKT细胞激活抗原的抗肿瘤潜力一直是基于NKT细胞的免疫疗法开发的重点。到目前为止，多项研究表明，给予糖脂（如α-半乳糖神经酰胺）可成功治疗某些转移性肿瘤。然而，应用这些抗原后会出现肝损伤。我们之前研究了使用β-葡萄糖神经酰胺（β-GlcCer）抑制肿瘤向肝脏转移的潜力。本研究的目的是确定β-GlcCer的抗转移作用及其对NKT细胞激活的影响。腹腔注射β-GlcCer可增强含NKT细胞的肝淋巴细胞产生干扰素-γ，并增加肝淋巴细胞对肿瘤细胞的细胞毒性。此外，给予β-GlcCer可抑制野生型（WT）小鼠肝脏中的肿瘤转移，但对CD1d（-/-）或Jα18（-/-）小鼠无效。连续2周每日给予β-GlcCer处理的WT小鼠未出现与其他糖脂相关的肝损伤缺点。本研究表明，β-GlcCer处理可激活不变NKT细胞，从而抑制肿瘤转移。
