科研之友
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摘要
Aim:
alpha-Galactosylceramide (alpha-GalCer) has been attracting attention as a novel approach to treat metastatic liver cancer. We investigated the detailed process of activating liver dendritic cells (DC) and immune cells after alpha-GalCer treatment in the mouse liver tumor model.
Methods:
BALB/c mice bearing CMS4 liver tumor (p53 peptide-expressing tumor) were treated by alpha-GalCer. We evaluated the activation of liver DC and immune cells after alpha-GalCer treatment. Interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assay was performed to detect p53 peptide-specific cytotoxic T lymphocytes (CTL). To assess the impact of systemic acquired immunity by alpha-GalCer treatment, 28 days after liver tumor treatment, CMS4 cells or Colon26 cells were re-challenged s.c.
Results:
The liver weights of alpha-GalCer-treated mice were significantly lighter than those of vehicle-treated mice. Depletion experiments revealed that natural killer (NK) cells were essential for the antitumor effect of alpha-GalCer. alpha-GalCer treatment significantly increased the population of DC and NK cells in the liver. The expressions of co-stimulatory molecules on liver DC significantly increased with the peak at 1 day after alpha-GalCer administration. IFN-gamma ELISPOT assay demonstrated that p53 peptide-specific CTL was generated efficiently in alpha-GalCer-treated mice. 51Cr-release assay revealed that CD8+, not CD4+, CTL against CMS4 cells were generated in alpha-GalCer-treated mice. The mice that had been protected from CMS4 liver tumor by alpha-GalCer injection became resistant against s.c. CMS4 re-challenge, but not against Colon26 re-challenge.
Conclusion:
These results demonstrated the therapeutic potential of alpha-GalCer against liver cancer through activating liver DC and immune cells in the liver.
- 出版日期2011-2
