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

Backgroud/Aims α-Galactosylceramide (α-GalCer) has been attracting attention as a novel approach to treat metastatic liver cancer. However, the activation of liver innate immunity by α-GalCer should be examined because clinical trials of α-GalCer resulted in limited clinical responses. Methods We examined the activation of liver innate immunity by α-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 α-GalCer treatment, the activation of these cells were significantly inhibited in C26s.c.TB-mice. α-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-β, 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-β, the recovery of CD1d expressions on liver DCs and the improvement of antitumor effect of α-GalCer against metastatic liver tumor. Conclusions These results suggested that tumor burden reduces CD1d expressions on liver DCs, thus impeding α-GalCer-mediated NK cell activation and antitumor activity in the liver.