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

Capacity of Specific Response of The TIL Activated Using T Cell Growth Factor in Malignant Ascites to Dendritic Cell Presenting Antigen

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 。

Objective Using T cell growth factor interleukin 2(IL 2) and phytahematoagglutinin (PHA) activated tumor infiltrating lymphocyte (TIL). Investigating IL 2 and PHA activated TIL combined with dendritic cells tumor antigen pulsed (DC Ag)infused into abdominal cavity of patients, to optimize local microenvironment of antigen presented, evaluating the feasibility of treat ment of ascites of advanced carcinoma patients with immunotherapy. Methods Ascites of advanced carcinoma patients were draw out to separate TIL and activated by IL 2 combined PHA. The density of IL 2R and IL 10R on TIL was analysed by FACS.after activated, the capacity of response to DC Ag presenting antigen was detected by 3H TdR mix into assay. Using IL 2 and PHA activated TIL combined with DC Ag which were infused into abdominal cavity of patients, to observe level of IFN γ in ascites and treat ment effects.Results IL 2R expressing on TIL was increased after activated while IL 10R was decreased, and the proliferated capacity of TIL to DC Ag was reinforced. The complete remission rate was 55.5%, part remission rate was 45.5%, and effectual rate was 100.0% in Immunotherapy suppress ascites. Level of IFN γin in treated ascites was (3 50±0 32)μg/mL,more increased than that in control group.Conclusions IL 2 and PHA can activate TIL, relieve suppressing effects of tumor cells to TIL, promote expression of Th1 cytokine receptor and reduce expression of Th2 cytokine receptor, enhance the responsive capacity of TIL to DC Ag presenting antigen, The infusion of IL 2 and PHA activated TIL combined with DC Ag into abdominal cavity can suppress malignant ascites effectively.