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

Abstract

BACKGROUND/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.

• Authors: Tomohide Tatsumi, Tetsuo Takehara, Shinjiro Yamaguchi, Akira Sasakawa, Masashi Yamamoto, Yui Fujita, Takuya Miyagi, Kazuyoshi Ohkawa, Norio Hayashi
• Journal: Journal of hepatology (J Hepatol) Vol. 49 Issue 5 Pg. 779-86 (Nov 2008) ISSN: 0168-8278 [Print] Netherlands
• PMID: 18760855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD1d
• Galactosylceramides
• Transforming Growth Factor beta
• alpha-galactosylceramide

Topics

• Animals
• Antigens, CD1d (metabolism)
• Cell Line, Tumor
• Dendritic Cells (immunology)
• Female
• Galactosylceramides (immunology, therapeutic use)
• Immunity, Innate
• Immunotherapy
• Killer Cells, Natural (immunology)
• Liver Neoplasms, Experimental (immunology, pathology, secondary, therapy)
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• Natural Killer T-Cells (immunology)
• Transforming Growth Factor beta (blood)
• Tumor Burden