结肠癌术后辅助免疫疗法抑制肿瘤腹腔转移的免疫机制

Promotion of additive immunotherapy on TRAIL expression of macrophages and sensitivity of neoplasms cells to chemotherapy after colon carcinoma surgery:A study on the mechanism of inhibiting intraabdominal tumor metastasis

目的探讨辅助免疫疗法促进小鼠腹腔巨噬细胞TRAIL表达,增强肿瘤细胞对化疗药物的敏感性,抑制肿瘤腹腔转移的免疫机制。方法用氟脲嘧啶(5-FU)治疗小鼠结肠癌转移模型,辅助免疫治疗,观察各组小鼠腹腔肿瘤生长情况,ELISA方法检测脾细胞培养物上清中分泌IFN-γ的水平,FSCA分析各组小鼠脾细胞内T淋巴细胞和NK细胞比例和腹腔巨噬细胞表面TRAIL的表达。结果化疗联合免疫治疗组小鼠腹腔未见肿瘤细胞生长,脾细胞内CD3+、CD4+、CD8+的T淋巴细胞和NK细胞比例明显增高,脾细胞培养物上清中分泌高水平IFN-γ,巨噬细胞表面诱导肿瘤细胞凋亡的TRAIL分子表达明显增强。结论结肠癌术后辅助性免疫治疗,能活化特异性CTL分泌IFN-γ,改善腹腔抗原提呈微环境,诱导肿瘤细胞凋亡,对化疗药物的敏感性显著增强,是有效抑制小鼠结肠癌腹腔转移的重要免疫机制。

Objective To investigate immune mechanism of inhibiting colon carcinoma abdominal cavity metastasis by immunotherapy,as well promoting TRAIL expression of the macrophages and enhancing sensitivity of neoplasms cells to chemotherapy after colon carcinoma surgery in mice. Methods The animal model of colon carcinoma metastasis in abdominal cavity were created, the tumor-bearing mice were treated with IL-2 abdominal cavity injection and CT26 colon carcinoma vaccine subcutaneous injection after 5-FU chemotherapy. Then, the therapeutic effects were observed, the level of excreted 1FN-γ by spleen cells were detected by MTT. Lymphoeytes of the spleen and expression of TRAIL on the macrophages were examined by FACS.Results The tumor growth was inhibited obviously,the excreted IFN-γ ability of spleen cells was promoted. The ratio of CD3^＋,CD4^＋,CD8T lymphocytes and natural kill cells were increased,the TRAIL on macrophage was up regulated in treated group with immunotherapy compared with other groups. Conclusion It is important immune mechanism that using immunotherapy could promote spleen cells excreting IFN-γand TRAIL expression on the macrophages, to optimize the anti-tumor microenvironment, induce tumor cells apoptosis and inhibit tumor metastasis in abdominal cavity, enhance the sensitivity of tumor cells to chemotherapy after colon carcinoma surgery.