期刊
LABORATORY INVESTIGATION
卷 94, 期 2, 页码 182-191出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2013.139
关键词
hepatic stellate cells; hepatocellular carcinoma; myeloid-derived suppressor cells; regulatory T cells
资金
- National Key Sci-Tech Special Project of China [2012ZX10002-011-005]
- National Natural Science Foundation of China [81171976, 81201894]
- Provincial Natural Science Foundation of Fujian, China [2011D003]
The immunosuppressive properties of hepatic stellate cells (HSCs) contribute to the occurrence and development of hepatocellular carcinoma (HCC). The accumulation of cells with immune suppressive activities, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) is a key mechanism for tumor immune evasion. However, the impact of HSCs on immune cell populations in tumor-bearing hosts is unclear. In this study, we established an orthotopic liver tumor mouse model for studying the complex tumor-host interactions in HCC. The activated HSCs promoted HCC growth not only induced tumor angiogenesis and lymphangiogenesis, but also significantly increased the suppressive immune cell population of Tregs and MDSCs in the spleen, bone marrow, and tumor tissues of the tumor-bearing mice. Murine HCC cell line H22-activated HSCs also expanded the expression of Tregs and MDSCs in vitro. In conclusion, our study suggests a novel role for HSCs in the HCC microenvironnnent. HSCs can promote HCC progression by enhancement of the immunosuppressive cell population. Targeting HSCs, which is a new concept in adjuvant immunotherapy, may be introduced in the near future to improve the outcome of patients with HCC.
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