Clinical Study Of Dendritic Cell Vaccine For Gastric Carcinoma

Objective: Dendritic cells are the most potential professional antigen presenting cells, which can innate immune response in body. But it was found that the quantities and immune function of the DCs of patients with tumor decreased significantly. A number of previous studies already demonstrated that dendritic cells vaccine can induce specific immune response against tumor and make tumor disappear in many animal tumor models. Some clinical trials had been done in patients with melanoma, prostate cancer or renal cell carcinoma and clinical effects had been evaluated . The aim of this study was to observe the changes of patients immune function and evaluate clinical effects of the DCs vaccine on gastric carcinoma patients.Methods: 1. Phenotype of the peripheral blood DCs of 47 patients with gastritic carcinoma and 18 controls was analysed by means of flowcytometry ; 2. Expression of IL-12 of DCs in tumor enviroment was detected by enzyme-linked immunosorbant assays (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Expression of immune molecules of DCs in tumor enviroment was detected by flowcytometry. Apoptosis of DCs in tumor enviroment was also observed by flowcytometry; 3.Twenty five patients with gastritic carcinoma were vaccined with dendritic cells pulsed with tumor antigen and T cell subsets of peripheral blood, Th1 type(IFN-γ)and Th2 type (IL-4)cytokines of these patients serum were detected at different time point. The cytokine secretion of PBMC after being activated by tumor antigens was tested. Delayed-type hypersensitivity (DTH) tests were also done.Results:1. The expressions of HLA-DR, CD80 and CD83 of peripheral blood DCs of patients with gastric carcinoma decreased obviously compared with those of controls. The immune function of peripheral blood DCs was significantly correlated with the TNM stage.2. Compared with those in control group, Expression of IL-12 of DCs in tumor enviroment was declined and expression of immunological molecules of DCs in tumor enviroment was decreased,too. Tumor cells can induce apoptosis of DCs significantly.3. We generated mature DCs from PBMC,which highly express HLA-DR, CD80 and CD83 and can strongly stimulate allogeneic lymphocytes in vitro.4. The ratio of CD4+T/CD8+T, the ratio of NK and levels of DFN-γ in patients serum increased after vaccination. The cytokine secretion of PBMC was enhanced after PBMC being activated by tumor antigens. Sixteen of 25 patients with gastritic carcinoma had a DTK response to tumor antigens after vaccination.5.No obviously side effects were found in all patients.Conclusion: The immunological function of the DCs from the peripheral blood in patients with gastric carcinoma decreased significantly. In vitro, the gastric carcinoma cells can suppress immunogical funtion of DCs in many aspects . We successfully produced DCs vaccine from PBMC ,which has efficient biological activity in vitro. Dendritic cells vaccine can improve patients immune status significantly and may be beneficial to clinical therapy of gastric carcinoma.