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[摘要]
观察肿瘤抗原致敏的树突状细胞联合白细胞介素2活化的淋巴细胞胸膜腹腔内输液治疗晚期癌性胸腹水的效果,为肿瘤的生物治疗提供新的思路。方法:分离晚期癌症患者外周血中单个核细胞,制备单核细胞来源的DC(MoDC)和IL-2活性的淋巴细胞。用患者胸腹腔积液中分离的肿瘤细胞制备冻融抗原致敏MoDC后,联合IL-2活化的淋巴细胞给患者胸腹腔输注,X线或B超监测免疫治疗后胸腹腔积液的变化,FACS分析治疗前后胸腹水中淋巴细胞表面细胞因子受体的表达情况,结果:经肿瘤抗原MoDC联合IL-2活化的淋巴细胞胸瘤腔输液后,胸腹水中表达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,光镜下可见较多的DC对淋巴细胞黏附及淋巴细胞对肿瘤细胞的杀伤,免疫治疗组完全缓解率46.9%,部分结解率53.1%,有效率100.0%,明显高于DDP对照组(P<0.05),结论:肿瘤抗原致敏的MoDC联合IL-2活化的淋巴细胞胸腹腔内输注能显著地促进胸腹水中肿瘤浸润性淋巴细胞的增殖和活化。提高了癌症患者的免疫功能,有效地治疗癌性胸腹水,其机制与肿瘤抗原致敏的MoDC对肿瘤抗原的有效提呈和IL-2活化的淋巴细胞对肿瘤细胞的直接杀伤作用有关。
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[Abstract]
To observe the curative effect of tumor antigen pulsed dendritic cells (DCs) combined with interleukin 2 (IL-2) activated lymphocytes infused into thoracic cavity and abdominal cavity on the inhibition of pleural fluid and ascites of advanced carcinoma patients, and to investigate the correlated immune mechanism. Methods: The peripheral blood mononuclear cells of patients suffered from advanced carcinoma were separated as a source of monocyte derived dendritic cells (MoDC) and IL-2-activated lymphocytes. MoDC were pulsed with tumor lysates derived from tumor cells of thoracic or abdominal fluid of patients, combined with IL-2-activated lymphocytes and infused into thoracic cavity and abdominal cavity of the patients. The changes of pleural fluid or ascites of patients were examined by X ray or B supersonic wave. The cytokine receptor on lymphocytes was analysis by FACS. Results: After Immunotherapy, the cancer cells in thoracic cavity and abdominal cavity of the patients were inhibited significantly. The expression of IL-2R on lymphocytes in pleural fluid and ascites was up-regulated and IL-10R was down-regulated. The complete remission rate was 46.9%, part remission rate was 51.3%, and effectual rate was 100 0% of patients received Immunotherapy. Curative effect was effective than that of DDP control( P <0.05). Conclusions: The DC pulsed with tumor antigen combined with IL-2-activated lymphocytes infused into thoracic cavity and abdominal cavity can effectively inhibit the growth of tumor cells. The mechanisms involved may be include: the first, DCs pulsed with tumor antigen may be effectively present the antigen to the T cells in pleural fluid and ascites, which can enhance the specific antitumor immunity; the second, IL-2 activated T cells may also be an effective effector to the tumor cells.
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