低剂量辐射增强小鼠肿瘤基因-放射治疗效应的免疫学机制研究

目的 探讨低剂量辐射全身照射对小鼠Lewis肺癌移植肿瘤基因-放疗方案中的免疫增强作用机制。方法 小鼠右后肢皮下接种Lewis肺癌细胞建立荷瘤模型,基因-放疗组中小鼠肿瘤局部注射由多聚乙烯亚胺包裹的pEgr-IL18-B7.1重组质粒,分别接受由2 Gy 局部照射和0.075 Gy 全身照射组合的不同治疗方案,通过³H-TdR标记方法检测小鼠CTL和NK细胞毒活性,ELISA方法检测TNF-α和IFN-γ分泌活性,观察各治疗组对荷瘤小鼠抗肿瘤免疫的作用。结果 在pEgr-IL18-B7.1基因治疗方案中,单次大剂量辐射局部照射后加多次低剂量全身照射与常规多次大剂量辐射局部照射相比,小鼠CTL和NK细胞毒活性显著增强,TNF-α和IFN-γ分泌活性有不同程度的增高。 结论 低剂量辐射可以通过促进CTL和NK细胞毒效应,上调TNF-α和IFN-γ细胞因子表达,从而增强机体抗肿瘤免疫功能,提高肿瘤基因-放疗的抑瘤效果。

Anti-tumor immunological mechanisms of low dose whole-body irradiation in the protocol of tumor gene-radiotherapy

Objective To investigate the immunologic enhancement of low dose whole-bedy irradiation in mice bearing Lewis lung carcinoma (LLC) under recombinant plasmid pEgr-IL18-B7.1 gene-radiotherapy.Methods LLC cells were implanted subcutaneously in the right-hind leg of C57BL/6J mice. The pEgr-IL18B7.1 recombinant plasmids mediated by polyethylenimine were injected locally into tumors of the mice with generadiotherapy, and then the tumors received different therapeutic regimens containing local irradiation with 2 Gy and whole-body irradiation with 0.075 Gy, respectively. Cytotoxic activity of CTL and NK were.detected with isotope labeling of 3 H-TdR. The secretion activities of TNF-α and IFN-γ were detected with ELISA. The anti-tumor immunological effects of low dose whole-bedy irradiation in protocol of gene-radiotherapy on the tumor-bearing mice were observed. Results Compared with conventional repeated high dose local irradiation, single high dose local irradiation in combination with repeated low dose whole-bedy irradiation could enhance the cytotoxic activity of CTL and NK, and increase the secretion of TNF-α and IFN-γ under pEgr-lL18-BT. 1 gene-radiotherapy. Conclusions Low dose whole-bedy irradiation superimposed upon a local high dose could significantly enhance the anti-tumor effect in the protocol of gene-radiotherapy through promoting the cytotoxic activity of CTL and NK, and up-regulating the expression of TNF-α and IFN-γ.