Decreased expressions of CD1d molecule on liver dendritic cells in subcutaneous tumor bearing mice
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Updated: Jul 2, 2026
Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
Tomohide Tatsumi1, Tetsuo Takehara, Shinjiro Yamaguchi
1Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
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.
Insights
Tumor burden in mice reduces CD1d expression on liver dendritic cells, hindering alpha-Galactosylceramide (alpha-GalCer) immunotherapy effectiveness against metastatic liver cancer. Reducing tumor mass restored immune activation and treatment efficacy.
Area of Science:
- Immunology
- Oncology
- Cancer Therapy
Background:
- Alpha-Galactosylceramide (alpha-GalCer) shows promise for metastatic liver cancer treatment.
- Limited clinical responses necessitate examination of alpha-GalCer's impact on liver innate immunity.
Purpose of the Study:
- To investigate the activation of liver innate immunity by alpha-GalCer in a mouse model of metastatic liver cancer.
- To understand the mechanisms behind limited clinical responses to alpha-GalCer therapy.
Main Methods:
- Examined alpha-GalCer's effect on liver innate immunity in subcutaneous Colon26 tumor-bearing mice (C26s.c.TB-mice).
- Assessed CD1d molecule expression on liver dendritic cells (DCs).
- Measured NK and NKT cell activation and serum TGF-beta levels.
Main Results:
- C26s.c.TB-mice exhibited lower CD1d expression on liver DCs compared to normal mice.
- alpha-GalCer treatment failed to activate NK and NKT cells in C26s.c.TB-mice, unlike in normal mice.
- Tumor burden increased serum TGF-beta, which suppressed CD1d expression and inhibited alpha-GalCer's antitumor effects.
Conclusions:
- Tumor burden downregulates CD1d expression on liver DCs.
- This downregulation impedes alpha-GalCer-mediated NK cell activation and antitumor activity in the liver.
- Reducing tumor mass can potentially restore immune function and enhance alpha-GalCer efficacy.
