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Updated: Jul 2, 2026
Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
Decreased expressions of CD1d molecule on liver dendritic cells in subcutaneous tumor bearing mice
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.
