Effects Of Tumor Cells On The Development And Function Of Human Dendritic Cell And The Underlying Mechanisms

Dendritc cell (DC) are the most potent professional antigen-presenting cell (APC) that display the unique function to sensitize naive T cells and induce anti-tumor activity of specific cytotoxic T lymphocytes (CTL). DC plays a pivotal role in the development of anti-tumor immunoreaction.The important role of DC in cancer has been emphasized by a number of reports that the presence of DC in tumor tissues was associated with good clinical prognosis of the diseases. Meanwhile, in recent years, several groups have described the defective function of DC in tumor-bearing mice and in cancer patients and in which both circulating and tumor-infiltrating DC are functionally impaired. These observations suggest that tumor cells possess mechanisms that allow them to escape initial immune recognition and futher destruction. Therefore, it will greatly enhance our understanding of tumor escape to studying the effects of tumor cells on the development and function of the mononuclear cell-derived dendritic cell (MoDC). Clarification of this mechanism was the purpose ofthis study.In this study, the supernatants of cultured cell lines H7402 (human hepatocellular carcinoma), HCT-8 (human colon carcinoma) and HFCL (human bone marrow stromal cell) were collected and used as the conditioned cultural medium (CCM) for MoDC culture. The dendritic cells were characterized by phenotypic analysis. We evaluated the ability to uptake dextran and stimulate allogeneic T cells of MoDC. Phenotypic analysis showed that dendritic cells cultured in the presence of supernatants of tumor cells expressed lower levels of CDla, MHO II molecules (HLA-DR) and costimulatory molecules (CD86), all of which were significantly lower than those in control and HFCL groups(the negative control group). Meanwhile, DCs expressed higher CD83 (a typical molecule of mature DC) than that cells of control and HFCL groups. Also, they displayed a much lower ability of phagocytizing dextran as shown by the FITOdextran assay. Moreover, they were less efficient of inducing allogeneic T-cell proliferation in a mixed lymphocyte reaction. We hypothesized that it might be the factors present in the tumor supernatants that interfere with the maturation and/or function of MoDC.Next, to prove our hypothesis, some immune inhibitors of tumor cells were detected by using RT-PCR. The results demonstrated that both H7402 and HCT-8 tumor cells expressed high level of VEGF and TGF-1. Howerver, addtion of VEGF andTGF- 1 did not induce similar results to the existence of supernatants of tumor cell lines. Based on these findings, we postulated that tumor cells release many kinds of soluble factors into their microenvironment, and they act together to regulate negatively the production and function of DC, which might be one of the underlying mechanisms that play a role in the immune escape of tumor cells.