Suppressive Effects of Transforming Growth Factor- 1 Produced by Hepatocellular Carcinoma Cell Lines on Interferon- Production by Peripheral Blood Mononuclear Cells

Transforming growth factor1 (TGF1)exerts potent immunosuppressive effects. In this study, we investigated the potential role of TGF1 produced by hepatocellular carcinoma(HCC)cell lines in immunosuppression mechanisms. Using the Mv1Lu cell-growth inhibition assay and an enzymelinked immunosorbent assay(ELISA), we detected optimal levels of TGF1 in the culture supernatants conditioned by the HCC cell lines PLC/PRF/5, Hep3B, and HepG2. To determine the biological activity of TGF1 in the supernatants, we examined the effects of the culture supernatants on the production of interferon (IFN)induced during the culture of peripheral blood mononuclear cells (PBMCs) stimulated with interleukin (IL)-12. IFNproduction of IL-12stimulated PBMCs in the 1:1 dilution of the acid-activated conditioned medium of PLC/PRF/5, Hep3B, and HepG2 reduced to 14.7±0.8, 17.3±9.0, and 35.9±14.6 , respectively, compared with the value in the culture with control medium(complete culture medium). These results suggest that HCC cells producing TGF1 may reduce the generation or activation of cytotoxic T lymphocytes (CTL)and natural killer(NK)cells, and thus could enhance their ability to escape immune-mediated surveillance.