α-Glycosylceramides enhance the antitumor cytotoxicity of hepatic lymphocytes obtained from cancer patients by activating CD3-CD56+ NK cells in vitro
α-Glycosylceramides enhance the antitumor cytotoxicity of hepatic lymphocytes obtained from cancer patients by activating CD3-CD56+ NK cells in vitro
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DOI：
10.4049/jimmunol.165.3.1659
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发表时间：
2000-08-01
影响因子：
4.4
通讯作者：
Juji, T
中科院分区：
文献类型：
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作者：
Ishihara, S;Nieda, M;Juji, T
α -半乳糖神经酰胺和α -葡萄糖神经酰胺等α -糖基神经酰胺可诱导多种小鼠肿瘤模型的抗肿瘤免疫。在小鼠肝转移模型中，优先在肝脏积累的V α 14 TCR(+)NK1.1(+) T细胞被认为在α -糖基神经酰胺诱导抗肿瘤免疫中起关键作用。我们最近报道了V α 24 TCR+ NKT细胞，小鼠V α 14 TCR(+)NK1.1（+）细胞的人类同源物，在新分离的人类肝淋巴细胞中很少见到。因此，研究α -糖基神经酰胺是否也增强了人类肝淋巴细胞的抗肿瘤细胞毒性，正如它们在小鼠系统中所显示的那样，以确定α -糖基神经酰胺在人类癌症免疫治疗中的有效性是很重要的。本研究表明，α -糖基神经酰胺可显著增强肿瘤患者肝淋巴细胞对肿瘤细胞系K562和Colo201的体外细胞毒性，其直接效应细胞为CD3(-)CD56(+) NK细胞。尽管V α 24 TCR+NKT细胞对α -糖基神经酰胺有显著的增殖反应，但它们并不直接参与细胞毒性。我们的观察结果强烈表明，基于α -糖基神经酰胺激活肝脏中CD3-CD56+ NK细胞的能力，α -糖基神经酰胺对人类肝癌免疫治疗的潜在有用性。
alpha-Glycosylceramides, such as alpha-galactosylceramide and alpha-glucosylceramide, induce antitumor immunity in various murine cancer models. In the murine hepatic metastasis model, V alpha 14 TCR(+)NK1.1(+) T cells, which accumulate preferentially in the liver, are considered to play a key role in the induction of antitumor immunity by alpha-glycosylceramides. We recently reported that V alpha 24 TCR+ NKT cells, the human homologues of murine V alpha 14 TCR(+)NK1.1(+)cells, are rarely seen among freshly isolated human hepatic lymphocytes, Therefore, it is important to examine whether alpha-glycosylceramides also enhance the antitumor cytotoxicity of human hepatic lymphocytes, as they have been shown to do in murine systems, to determine the usefulness of alpha-glycosylceramides in cancer immunotherapy in humans. Here, we show that alpha-glycosylceramides greatly enhance the cytotoxicity of human hepatic lymphocytes obtained from cancer patients against the tumor cell lines, K562 and Colo201, in vitro, The direct effector cells of the elicited cytotoxicity were CD3(-)CD56(+) NK cells. Even though V alpha 24 TCR+NKT cells proliferated remarkably in response to alpha-glycosylceramides, they did not contribute directly to the cytotoxicity. Our observations strongly suggest the potential usefulness of alpha-glycosylceramides for immunotherapy of liver cancer in humans based on their ability to activate CD3-CD56+ NK cells in the liver.