| Background: Renal cell carcinoma is one of common malignant tumors of the urinary system, RCC early clinical manifestations are more hidden, 25%-57% of the patients diagnosed with metastasis, about 20%-30% of the patients with localized renal cell carcinoma will continue to develop into metastatic cancer. Renal cell carcinoma has multiple drug resistance genes, a large number of studies at home and abroad show that renal cell carcinoma is not sensitive to conventional radiotherapy and chemotherapy. 5-year survival rate is less than 15%, the median survival time(OS) is only 10.2 months. RCC is a highly immunogenic tumor, biological treatment has been the optional treatment method in first-line treatment options. Early cytokine therapy, including high dose of IL-2 and interferon alpha showed certain effect, but the difficulty to control the dose toxicity limit its clinical application.With the development of molecular targeted drug research, including sorafenib and sunitinib,and other small molecule TKI targeted drugs are used to treat metastatic renal cell carcinoma, and gradually replaced the early cytokine therapy. In recent years, domestic and foreign clinical trial results showed that the objective effective rate of sorafenib in the treatment of metastatic renal cell carcinoma was 24%, the median OS was 29.3 months,the objective effective rate of sunitinib in the first-line treatment of metastatic renal cell carcinoma was 31.1%, disease control rate was 76.7%, the median OS was 30.7 months. But the molecular targeted drug side effects and drug resistance problems remain to be solved.Based on these reasons,the treatment of metastatic renal cell carcinoma is challenging, so look for newer and more effective ways to treat patients with metastatic renal cell carcinoma has become the focus of research.Cell immunotherapy is developed in recent years, with high safety, can effectively eliminate minimal residual tumor lesions as the main characteristics, its mechanism is through enhancing the body’s immune function, improving the body’s immune suppressed state, improving the anti-tumor immunity in patients reaction, so as to kill tumor cells and control the tumor cell growth, also does not damage normal cells. Cellular immune therapy is a new anti-tumor therapy mode developed in recent years,following the surgery, chemotherapy, radiation therapy,has become a focus in the field of metastatic renal cell carcinoma treatment. In recent years, our hospital use DC-CIK cells to treat renal cell carcinoma has achieved good clinical efficacy.Objective: To evaluate the clinical efficacy,immune function and follow-up observation of dendritic cells and cytokine-induced killer in the treatment of metastatic renal cell carcinoma. To discuss the clinical application value of DC-CIK cell immunotherapy of metastatic renal cell carcinoma,and the preliminary study on its mechanism of action.To provide new ideas for the treatment of patients with metastatic renal cell carcinoma and provide clinical data for security applications for the DC-CIK treatment of metastatic renal cell carcinoma.Methods: Observed the 27 evaluable patients with metastatic renal cell carcinoma which treated by our hospital from January 2011 to May 2013, Among them, 23 cases were male and 4 cases were females, aged 32-81 years, with a median age of 57 years,The KPS score 70-90 points. All patients were treated with standard regimen, their pathological types were renal clear cell carcinoma, and they were treated for more than 2 courses of treatment, also were received periodic review after treatment.Collected the patients’ peripheral blood mononuclear cells(PBMC),induced generation of DC and CIK cells by laboratory in vitro culture.After sterility test,phenotypic characterization of flow cytometry and cell count, returned to the patient.Treated patients with subcutaneous injection(3-10) x 107 DC(1ml) after collected PBMC on days 7,9,11,13 and intravenous transfusion(2-15) × 109 CIK cells(100ml) on the days 11, 13. This treatment regimen was repeated at an interval of 3 months until the disease progresses.Observed the clinical efficacy and adverse reactions,metastatic sites and the relationship between immune therapy and clinical clinical efficacy. Main observation indexes were the objective response rate( ORR), disease control rates(DCR), and 2 years overall survival(OS) rate. Secondary outcome were the incidence of adverse reactions and the factors influencing patients’ OS.Take the patients’ peripheral blood one week before treatment and one months after the completion of each course’s treatment to detect lymphocyte subgroup results by flow cytometry, including CD3 +CD4+CD8- and CD3+CD4-CD8+ and CD3+CD19-, CD3-CD19+ and CD3-CD16+CD56+, CD3+CD16+CD56+ and CD3+HLA-DR- and CD3+HLA-DR+ and CD3+CD8+CD28+ and CD3+CD4+CD25+, the change of Th1 and Th2. Compared the change of lymphocyte subgroup level before and after treatment, preliminary study on the mechanism of cellular immunotherapy. Using SPSS19.0 software to analyze all the data, Used variance analysis to analyze the changes of lymphocyte subsets in different time points before and after cell immunotherapy, P < 0.05 indicate the difference was statistically significant.Results: Through DC-CIK therapy, among 27 cases of patients with metastatic RCC, 1 case of CR(3.7%), 9 cases of PR(33.3%), 13 cases of SD(48.2%), 4 cased of PD(14.8%);objective response rate was 37% and the disease control rate was 85%, 2 year overall survival rate was 81.5%. Th1 cells in peripheral blood of patients with cellular immune therapy had an increased tendency(P < 0.05).After several treatment, CD3+CD4+ CD25+ T cells(Treg cells) tended to decrease(P<0.05),CD3+CD4+CD8-,CD3+CD4-CD8+,CD3+CD19-,CD3-CD19+,CD3-CD16+C D56+,CD3+CD16+CD56+,CD3+HLA-DR-,CD3+HLA-DR+,CD3+CD28+CD8+ cell subsets and Th2 had no significant change(P> 0.05) after treatment compared with before treatment.Conclusion: 1.DC-CIK cell immunotherapy is safe and effective for treatment of metastatic renal cell carcinoma;2.After DC-CIK cells immunotherapy,In immune function, CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD19- and CD3-CD19+, CD3-CD16+CD56+, CD3+CD16+CD56+, CD3+HLA-DR- and CD3+HLA-DR+, CD3+CD28+CD8+ cell subsets and Th2 had no significant change after treatment compared with before treatment.After multiple DC-CIK cells immunotherapy Treg cells decline, Th1 cells rise, DC-CIK cells immunotherapy has inhibitory effect on Treg cells, can improve patients with metastatic kidney cancer immunosuppressive state, improve the antitumor immune responses of patients. |
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