T细胞生长因子活化癌性腹水中TIL对树突状细胞抗原提呈的应答能力

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目的 :用T细胞生长因子白细胞介素 2 (IL 2 )和植物血凝素 (PHA)活化癌性腹水中肿瘤浸润的淋巴细胞 (TIL) ,联合肿瘤抗原致敏的树突状细胞 (DC Ag)腹腔回输 ,探讨对腹腔抗原提呈微环境的优化作用 ,评估免疫治疗晚期癌性腹水的可行性。方法 :从晚期癌症患者腹腔积液中分离TIL ,用小剂量IL 2和PHA活化 ,流式细胞仪 (FACS)分析TIL表面IL 2R和IL 10R的变化 ;3H TdR掺入法检测TIL对DC Ag抗原提呈的增殖能力 ;腹腔回输后观察腹水中IFN γ的含量变化和对恶性腹水的治疗效果。结果 :癌性腹水中分离的TIL经IL 2和PHA活化后 ,细胞表面表达IL 2R的淋巴细胞数目明显增多 ,表达IL 10R的淋巴细胞数目明显减少 ,活化后的TIL对DC Ag的增殖能力增强 ;腹水中IFN γ的含量为 (3 5 0± 0 32 ) μg mL ,明显高于对照组 ;免疫治疗的完全缓解率 5 4 .5 % ,部分缓解率 4 5 .5 % ,总有效率 10 0 %。结论 :IL 2能有效地解除肿瘤细胞对淋巴细胞的抑制作用 ,促进TIL表面的Th1型细胞因子受体的表达 ,降低Th2型细胞因子受体的表达 ,增强对DC Ag的免疫应答能力 ,联合DC Ag腹腔回输 ,能有效地治疗恶性腹水 OBJECTIVE: To activate tumor-infiltrating lymphocytes (TILs) in cancerous ascites with T cell growth factor interleukin 2 (IL 2) and phytohemagglutinin (PHA), and to combine dendritic cells (DC Ag ) Intraperitoneal transfusion, to explore the optimization of the peritoneal antigen presentation microenvironment, to evaluate the feasibility of immunotherapy for advanced cancerous ascites. Methods: TIL was isolated from peritoneal effusion of patients with advanced cancer, activated with low dose of IL 2 and PHA, the changes of IL 2R and IL 10R on TIL were analyzed by flow cytometry (FACS); the effect of TIL on DC Ag Antigen-presenting proliferative capacity; changes in the content of IFN-γ in ascites and the therapeutic effect on malignant ascites after intra-abdominal transfusion. RESULTS: The TILs isolated from cancerous ascites were activated by IL-2 and PHA, the number of lymphocytes expressing IL-2R on the cell surface was significantly increased, the number of lymphocytes expressing IL-10R was significantly decreased, and the activated TIL enhanced the proliferation of DC Ag ; The level of IFN γ in ascites was (35 ± 0 32) μg mL, which was significantly higher than that of the control group. The complete remission rate of immunotherapy was 54.5%, the partial remission rate was 45.5% and the total effective rate was 10 0%. Conclusion: IL 2 can effectively relieve the inhibitory effect of tumor cells on lymphocytes, promote the expression of Th1-type cytokine receptors on TIL, decrease the expression of Th2-type cytokine receptors and enhance the immune response to DC Ag. DC Ag abdominal transfusion, can effectively treat malignant ascites
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