Palliative Postoperative Autologous Adoptive Multiple-cellular Immunotherapy In Advanced Digestive Cancer

Objective:(1) to investigate the cytotoxicity in vitro and antitumor efficacy in vivo of cytokine-induced killer(CIK) cells after coculturing with autologous dendritic cells(DCs).(2) to evaluate the therapeutic effect of autologous cytokine-induced killer cells in combination with dendritic cells in palliative postoperative advanced pancreatic cancer.(3) to establish the method of combined with minimally invasive approaches to peritoneal cavity or local region injection of DC-CIK cells in postoperative digestive cancer patients.Method:(1) DCs and CIK cells were induced in vitro, determined the phenotype of cytokine-induced killer cells co-culturing with autologous dendritic cells(DC-CIK cells) and the cytotoxicity through LDH assay.(2) 35 patients with palliative postoperative advanced pancreatic cancer were divided into two groups: Palliative and Palliative+adoptive immunotherapy.Adoptive immunotherapy group consisted of 13 patients.The survival time,clinical benefit response(CBR), progression-free time(PFS),CA19-9 and side effects was evaluated,and the factors influencing survival were analyzed using unviviate(log-rank) methods.(3) combined with DS.A and T.ACE,with laparoscopy,with the da Vinci Robotic Surgery system, DC-CIK cells were transfused via hepatic artery to the patients.Under ultrasonography, or via intraoperative ultrasonography for detecting the lesions,the DC-CIK cells were injected into the local lymph nodes,or peritoneal cavity.Results:(1) autologous DCs co-cultured CIK cells had a significant increase in cytotoxic activity against tumor cells compared with CIK cells without co-culture,that is 100%at an effector-to-target ratio of 10:1(p＜0.01).(2) in palliative postoperative advanced pancreatic cancer patients, The median survival time was 8 months and the overall 1-year survival rate was 26%. The median survival time and 1-year survival rate were 12 months and 50%in immunotherapy;4 months and 8%in Palliative group respectively.There was significant difference between Palliative+adoptive immunotherapy and palliative group(p＜0.01).CBR(62%) of Palliative-adoptive immunotherapy group was compared with the palliative group(45%),there was also significant difference between the two groups(p＜0.05).(3) 2 patients with TACE and transfused via hepatic artery,3 patients with laparoscopy,2 patients with the da Vinci Robotic Surgery system,120 patients with peritoneal cavity injection ultrasonography.Conclusion:(1) there was a significant cytotoxicity in vitro and antitumor efficacy in vivo of cytokine-induced killer(CIK) cells after coculturing with autologous dendritic cells(DCs).(2) combined with pallivative surgery and adoptive immunotherapy focused on improving living quality,controlling progression of disease,prolonging survival time.(3) combined with minimally invasive approtches can give patients the results of shorter recovery,less postoperative pain,reduced overall cost and improved surgical outcomes.From a clinical point of view,it is worth applying DC-CIK based immunotherapy to the treatment of advanced pancreatic cancers.