Study On The Treatment By Chemotherapy Combined With CIK Cells Of Stage Ⅲ Gastric Cancer

Objective To generate cytokine-induced killer (CIK) cells by inducing lymphocytes cells from peripheral blood in vitro, and study the immune phenotype and cytotoxic activity of CIK; then evaluate the clinical efficacy of the treatment of postoperative advanced gastric cancer by chemotherapy combined with cytokine-induced killer cells.Methods The peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Conray density gradient centrifugation. PBMCs were activated with IFN-γ, rhIL-2, rhIL-1α, anti-CD3McAb. The phenotype of CIK cells were analyzed by FACS, and the cytotoxic activity were tested by MTT. A total of eighty eight patients of stage III gastric cancer who received six cycles of chemotherapy after radical gastrectomy were followed-up. Among of them,forty five patients received chemotherapy alone (thirty patients treated by combined regimen included oxaliplatin and fifteen patients by docetaxol); forty three patients received additional CIK cells transfusion after chemotherapy (twenty nine patients treated by combined regimen included oxaliplatin and forteen patients by docetaxol). The disease-free survival time and overall survival time were compared between the two groups by long-rank test. In addition, the change of T-cell subgroup after CIK transfusion was observed in the study.Results①The number of CIK was increased significantly during cell culture, reaching the highest on day 14 to 21. The cytotoxic activity of the CIK cells to K562 and Raji was highest on day 14, (76.65±16.78)% and (75.32±15.61)% respectively. CD3+ T cells and the ratio of CD4+/CD8+ significantly increased after CIK transfusion in the 2nd week, then recovered to the level closed to pre-transfusion, and maintained on relative high level after more than 3 cycles of transfusion thereafter. The median overall survival time of patients of chemotherapy combined with CIK group and chemotherapy alone were 41months (95%CI:33.6-48.4 months) and 37months (95%CI:27.9-40.1months) respectively. The median disease-free survival time of these two groups were 27 months (95%CI:23.1-32.9 months) and 22 months (95%CI:19.9-30.1 months), respectively. Patients in chemotherapy combined with CIK group had significantly longer overall survival time (χ2=4.055, P=0.044) and disease-free survival time (χ2=4.480,P=0.034) than patients in chemotherapy alone group.Conclusions Both the cell number and cytotoxic activity were highest on day 14, and these CIK cells were suitable for transfusion into the patients. In patients of stage III gastric cancer with surgical resection, CIK transfusion could improve the immunologic function of patients after chemotherapy, and may prolong overall and disease-free survival.