title: Decreased expressions of CD1d molecule on liver dendritic cells in subcutaneous tumor bearing mice.
abstract: OBJECTIVE
  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.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Sasakawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yui
authors.initials: Y
authors.lastname: Fujita
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyagi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ohkawa
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi