| BackgroundPrimary hepatocellular carcinoma is one of the most common human malignancies,it occurs when a tumor develops from hepatocytes or biliary epithelia cells within the liver. It poses one of the major threat to human health, which accounts for 600 thousand deaths worldwide. In our country, PHC is becoming the second leading cause of cancer death. Besides, the incidence of primary hepatocellular cancer in the elderly continues to rise as the population ages. Surgery is the first strategy for the majority of patients with liver cancer, providing a5-year survival rate up to 70% in certain cases who undergo an operation following strictindication. But because of the special situation of our country,lots patients have missed the best chance of treatment when come to hospital,and could only accept transcatheter arterial chemoembolization,radio frequency ablation or liver transplantation operation treatment,the clinical curative effect is not ideal,even harm patient’s immunologic function.With the rapid development of tumor immunology and deepening research of clinical immunotherapy, immunotherapy has become a new method of cancer treatment.CIK cells are cytokine-induced killer cells,they are new type of immune cells. They are collected from the peripheral blood mononuclear cells, induced by varieties of cytokines in vitro.It was development by Schmidt-Wolf in Stanford University in 1991.It is a kind of CD3+CD56+ double positive cytotoxic cells,and not only have the anti-cancer function of T lymphocyte, but also with thenon-MHC restriction inhibition advantage of NK cell. CIK cells have the advantages of proliferation rapidly, powerful activity and they also have effect on multidrug resistance tumors. However,they have no effect on normal cells.It has been the fourth method in treatment of PHCafter operation,radiotherapy and chemotherapy. Although the method of obtaining little peripheral blood monocyte cells and culter them ex vivounder specific condition,then transfuse the CIK cells to patients has show significant clinical effect,but the influence factors of curative effect are not clear,and effective molecular targets to predict efficacy is lacking.ObjectiveTo explore the clinical efficacy of cytokine-induced killer cells immunotherapy inprimary hepatocellular carcinoma,analyze the influence of immunologic function and recurernce rate,aim to improve primary hepatocellular carcinoma patient’s prognosis.Methods54 cases of primary hepatocellular carcinoma from September. 2012 to September. 2014 in Chongqing Southwest Hospital were in the study.All cases’ stage were Ⅰ,Ⅱ and Child-pugh level were A and B,35 cases were male, 19 were female,44 to 79 years old.All the diagnosis of patients were based on clinical symptoms, B ultrasound and pathology inspection.Make sure that immunosuppressive agents and hormone drugs were not used before treatment.54 cases were divided into two groups according CIK treatment after operation.treatment group(27 cases) accept CIK treatment for 2 courses and control group(27 cases) accept conventional therapy.Follow up all cases at least 62 weeks,and use flow cytometry detect Myeloid-derived suppressor cells,dendritic cells,Regulatory cell and tumor-associated macrophage in peripheral blood.50 cases healthy human had physical examination meanwhile were compared.Collected the data of recurernce rate at last follow up.Statistical analysis by SPSS 20.0,using T test and chi-square test to analysis data.ResultsThe level of CD3+,CD8+,CD3+CD8+ and CD3+CD56+ in CIK cell were higher than those before inducted in culture for 14 days,but the level of CD4+,CD3+CD4+ and CD3-CD56+ were lower,P<0.05.The level of CD3+ and CD4+/CD8+ in peripheral blood of PHC in treatment group and control group was higher than that of healthy group before treatment,the level of CD8+ was lower,P<0.05.After 2 courses of CIK treatment,the level of CD8+ in treatment group was higher and CD4+/CD8+ was lower,P<0.05.As flow cytometry analyzed,peripheral blood MDSCs cells,TAM cells and Treg cells accounted for the percentage of monocytes were higher than health group before treatment in both treatment group and control group,but DC1/DC2 was lower, P < 0.05.After treatment,peripheral blood MDSCs cells and Treg cells accounted for the percentage of monocytes were lower in both treatment group and control group,peripheral blood TAM cells accounted for the percentage of monocytes was lower,but DC1/DC2 was higher in treatment group,P< 0.05.The comparison between groups after treatment showed that peripheral blood MDSCs cells,TAM cells and Treg cells accounted for the percentage of monocytes in treatment group were lower than control group,DC1/DC2 was higher, P<0.05.Treatment group recurrence rate was lower than health group(11.1% vs 33.3%,P<0.05).But there were no statistical difference in mortality rates in two groups(11.1% vs 18.5%,P>0.05).There were 5 cases of patients with low fever in treatment group and self healing in 4 days.ConclusionsThe immune functions of primary hepatocellular carcinoma patients were decreased and related to recurrence rate,it could be enhanced by CIK immunotherapy. The flow cytometry is a rapid,sensitive and accurate method to detect the immunological function of patients with Primary hepatocellular carcinoma and is an effective evaluation method of CIK therapy. |
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