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目的证实树突状细胞(dendritic cells,DC)可在体内通过吞噬凋亡肿瘤细胞获取抗原物质,探讨其在肿瘤免疫治疗中的意义。方法以615小鼠的前胃癌细胞株造模,在体外用rmGM-CSF和rm IL-4从荷瘤小鼠骨髓细胞分化、诱导未成熟树突状细胞。分为4组:小剂量化疗组、树突状细胞组、小剂量化疗+树突状细胞组和对照组,以BAX试剂盒检测肿瘤细胞凋亡。在瘤体内注射树突状细胞,观察给药侧瘤体及对侧瘤体体积,生存期,和特异性细胞毒性T淋巴细胞(CTLs)对肿瘤细胞的特异性杀伤作用。结果小剂量化疗能诱导肿瘤细胞凋亡。小剂量化疗后瘤内应用树突状细胞,给药侧瘤体及对侧瘤体体积明显缩小(P<0.05),小鼠的生存率提高,体内凋亡肿瘤细胞致敏的DC诱导的CTL对MFC有显著的杀伤作用,在效靶比为40∶1、20∶1、10∶1和5∶1时72 h的杀伤率分别为87.64%、70.32%、34.63%和13.87%。并能特异性杀伤小鼠前胃癌细胞MFC(P<0.01)。结论体外诱导分化的未成熟DC,能于体内捕获小剂量化疗诱导的凋亡肿瘤细胞所携带的肿瘤抗原,诱导机体特异性抗肿瘤免疫反应。
Objective To confirm that dendritic cells (DCs) can phagocytose apoptotic tumor cells to obtain antigenic substances in vivo and discuss its significance in tumor immunotherapy. Methods 615 mice were used to establish a model of precancerous gastric cancer cell line. In vitro, rmGM-CSF and rm IL-4 were used to differentiate and induce immature dendritic cells from tumor-bearing mouse bone marrow cells. They were divided into 4 groups: low-dose chemotherapy group, dendritic cell group, low-dose chemotherapy + dendritic cell group and control group. BAX kit was used to detect tumor cell apoptosis. The dendritic cells were injected into the tumor to observe the tumor volume, contralateral tumor volume, survival time, and the specific killing effect of specific cytotoxic T lymphocytes (CTLs) on tumor cells. Results Low dose chemotherapy can induce apoptosis of tumor cells. After low-dose chemotherapy, dendritic cells were applied intratumorally. The volume of tumors on the administration side and contralateral tumors were significantly reduced (P<0.05). The survival rate of the mice was increased, and DC-induced CTLs sensitized to apoptotic tumor cells in vivo. There was a significant killing effect on MFC. The 72 h kill rates at the effect ratios of 40:1, 20:1, 10:1, and 5:1 were 87.64%, 70.32%, 34.63%, and 13.87%, respectively. And can specifically kill mice MFC (P <0.01). Conclusion In vitro induced differentiation of immature DCs can capture tumor antigens in tumor cells induced by low-dose chemotherapy and induce specific anti-tumor immune responses.