Functional impairment of dendritic cells caused by murine hepatocellular carcinoma.
Immunosuppression in tumor-bearing hosts may be a major obstacle in eradicating tumors. This study investigated whether hepatocellular carcinoma suppressed the functions of dendritic cells to escape tumor surveillance. Dendritic cells (DC), propagated from C57BL/10J mice, were cocultured with or without murine hepatoma Hepa1-6 cells to examine the influence of hepatocellular carcinoma on dendritic cells. The results revealed that dendritic cells cocultured with hepatoma cells expressed low levels of costimulatory molecules, and the stimulatory capacity was decreased. The antigen-specific cytotoxic effects of T cells activated by the DC cocultured with hepatoma cells were also decreased. In ex vivo studies, the maturation and function of dendritic cells propagated from tumor-bearing mice were suppressed. The suppressive effect of Hepa1-6 cells on dendritic cells could be partially reversed by neutralizing IL-10. In conclusion, the maturation and stimulatory function of DC are suppressed by hepatocellular carcinoma. IL-10 release may be one of the mechanisms employed by hepatocellular carcinoma to suppress dendritic cells.
Lee
Wei-Chen
WC
Laboratory of Immunology, Department of General Surgery, Chang-Gung Memorial Hospital, Taipei, Taiwan. weichen@cgmh.org.tw
Chiang
Yang-Jen
YJ
Wang
Hui-Chuan
HC
Wang
Min-Ru
MR
Lia
Shin-Ru
SR
Chen
Miin-Fu
MF
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D005802:Genes, MHC Class II / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000276:immunology / Q000503:physiopathology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000951:Antigens, Neoplasm; D016753:Interleukin-10