Decreased expressions of CD1d molecule on liver dendritic cells in subcutaneous tumor bearing mice

被引:4
|
作者
Tatsumi, Tomohide [1 ,2 ,3 ]
Takehara, Tetsuo [1 ,3 ]
Yamaguchi, Shinjiro [1 ,3 ]
Sasakawa, Akira [1 ,3 ]
Yamamoto, Masashi [1 ,3 ]
Fujita, Yui [1 ]
Miyagi, Takuya [1 ]
Ohkawa, Kazuyoshi [1 ]
Hayashi, Norio [1 ,3 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Suita, Osaka 5650871, Japan
[2] Osaka Univ Hosp, Med Ctr Translat Res, Suita, Osaka 5650871, Japan
[3] Japan Sci & Technol Agcy, CREST, Tokyo 1500002, Japan
基金
日本科学技术振兴机构;
关键词
alpha-Galactosylceramide; CD1d; Liver dendritic cells; Antitumor immunity;
D O I
10.1016/j.jhep.2008.06.011
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Backgroud/Aims: alpha-Galactosylceramide (alpha-GalCer) has been attracting attention as a novel approach to treat metastatic liver cancer. However, the activation of liver innate immunity by alpha-GalCer should be examined because clinical trials of alpha-GalCer resulted in limited clinical responses. Methods: We examined the activation of liver innate immunity by alpha-GalCer in subcutaneous Colon26 tumor bearing-mice (C26s.c.TB-mice). Results:The expressions of CD1d molecule on liver dendritic cells (DCs) were significantly lower in C26s.c.TB-mice than those in tumor-unbearing normal mice. Although liver NK cells and NKT cells activated in normal mice after alpha-GalCer treatment, the activation of these cells were significantly inhibited in C26s.c.TB-mice. alpha-GalCer treatment resulted in significant antitumor effect against Colon26 metastatic liver tumor in normal mice, but not in C26s.c.TB-mice. The serum levels of TGF-beta, known to suppress the CD1d expressions on DCs, in C26s.c.TB-mice were significantly higher than those in normal mice. Surgical subcutaneous tumor mass reduction resulted in the reduction of serum TGF-beta, the recovery of CD1d expressions on liver DCs and the improvement of antitumor effect of alpha-GalCer against metastatic liver tumor. Conclusions: These results suggested that tumor burden reduces CD1d expressions on liver DCs, thus impeding alpha-GalCer-mediated NK cell activation and antitumor activity in the liver. (C) 2008 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
引用
收藏
页码:779 / 786
页数:8
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