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目的 探讨主要组织相容性复合物 (MHCI)类肿瘤抗原多肽体外致敏、白细胞介素(IL) 2基因修饰的树突状细胞 (DC)对小鼠恶性肿瘤切除术后自发性肺转移的体内抑制效果及相关免疫机制。方法 用小鼠Lewis肺癌 3LL细胞株MHCI类肿瘤抗原八肽Mut1致敏IL 2基因修饰的DC(DC IL 2 Mut1) 2× 10 6/ml免疫小鼠 ,用 3LL细胞每只 5× 10 6/ml皮下荷瘤 ,观察免疫保护情况 ;并用抗CD4 + 、CD8+ 和NK1.1+ 单克隆抗体体内阻断免疫细胞亚群 ,探讨DC IL 2 Mut1在小鼠体内诱导的特异性抗肿瘤机理。用DC IL 2 Mut1给小鼠肿瘤自发性肺转移模型尾静脉注射 ,观察对肺转移的抑制效果。结果 免疫小鼠荷瘤后第 2 0天 ,磷酸盐缓冲液 (PBS)对照组肿瘤直径为 ( 2 0 .0± 2 .0 )mm ,DC IL 2 Mut1免疫组未见肿瘤生长。抗CD8+ 单克隆抗体能部分阻断其免疫保护作用 ,而抗CD4 + 和CD8+ 单抗联合应用 ,能完全阻断DC IL 2 Mut1在小鼠体内诱导的特异性免疫效应 ,抗CD4 + 和抗NK+ 细胞单抗有一定的阻断效果。荷瘤截肢术后 2 0d ,对照组小鼠肺重量为 ( 110 5 .0± 113.0 )mg ,肺表面转移结节为 ( 4 8.8± 4.5 )个 ;DC IL 2 Mut1组肺重为 ( 2 13.0±2 8.5 )mg,肺表面肉眼未能看到转移结节 ,生存期较其他各组明显延长。结论 IL 2基因修饰能
Objective To investigate the in vitro sensitization of primary histocompatibility complex (MHCI) class tumor antigen peptides and dendritic cells (DC) modified by interleukin (IL) 2 gene in spontaneous lung metastasis after resection of malignant tumors in mice. In vivo inhibition and related immune mechanisms. METHODS Mice were immunized with IL-2 gene-modified DC (DC IL 2 Mut1) 2×10 6 /ml with mouse Lewis lung carcinoma 3LL cell line MHC class I tumor antigen octopeptide Mut1 and 3×10 6 cells per 3LL cells. The mice were subcutaneously implanted with tumors to observe the immune protection. The anti-CD4+, CD8+, and NK1.1+ mAbs were used to block immune cell subsets in vivo to investigate the specific anti-tumor mechanisms induced by DC IL 2 Mut1 in mice. DC IL 2 Mut 1 was injected into the tail vein of a mouse model of spontaneous lung metastasis to observe the inhibitory effect on lung metastasis. Results On the 20th day after the tumor-bearing mice were immunized, the diameter of the tumor in the phosphate buffered saline (PBS) control group was (2 0 .0± 2.0) mm, and no tumor growth was observed in the DC IL 2 Mut1 immune group. The anti-CD8+ mAb partially blocked its immunoprotective effect, whereas the combination of anti-CD4 + and CD8+ mAb completely blocked the specific immune effects induced by DC IL 2 Mut1 in mice, anti-CD4 + and anti-NK+ Cellular monoclonal antibody has a certain blocking effect. After 20 days of tumor-bearing amputation, the lung weight of the control group was (1105.0 ± 113.0) mg, and the surface metastatic nodules of the lung were (48.8 ± 4.5); the lung weight in the DC IL2 Mut1 group was (2 13.0). ±2 8.5 mg. The metastatic nodules were not visible to the naked eye on the lung surface, and the survival time was significantly longer than that in the other groups. Conclusion IL 2 gene modification