CAJ | 학술논문

目的：建立具有人免疫学特征的NOD/SCID小鼠模型，并观察其对三阴乳腺癌的免疫应答。方法筛选无免疫渗漏NOD/SCID小鼠24只，分成4组，免疫重建组提前3 d腹腔注射250 mg/kg环磷酰胺（CTX），后经腹腔注射健康人外周血单个核细胞（PBMC）同时背部皮下接种人三阴乳腺癌细胞MDA-MB-231；单纯免疫组只注射CTX及PBMC；单纯荷瘤组只接种MDA-MB-231；空白对照组不作任何处理。定期观察各组小鼠生物学及免疫学特征。结果免疫荷瘤组成瘤潜伏期（10~12 d）较单纯荷瘤组（8~10 d）延长，肿瘤生长速度减缓，第5周末肿瘤体积分别为1244.82±792.82 mm3和4308.77 mm3（P<0.01），生存率提高（P<0.01）。接受免疫重建的小鼠外周血人IgG于第2周即可测到，并逐渐上升，较未接受免疫重建小鼠差异有统计学意义（P<0.01）。外周血中CD3+细胞比例于第2周逐渐下降，但于第9周仍可测到。第9周小鼠脾脏细胞中CD3+T细胞比例高达55.3%（免疫荷瘤组）及52.7%（单纯荷瘤组）。免疫荷瘤组小鼠脾指数9.64 mg/g明显高于单纯免疫组3.82±0.31 mg/g及空白对照组1.51±0.14 mg/g。结论成功构建稳定的具有人免疫学特征的NOD/SCID小鼠模型，并观察到其对三阴乳腺癌产生免疫应答，可为三阴乳腺癌免疫治疗研究提供较为理想的动物模型。
목적：건립구유인면역학특정적NOD/SCID소서모형，병관찰기대삼음유선암적면역응답。방법사선무면역삼루NOD/SCID소서24지，분성4조，면역중건조제전3 d복강주사250 mg/kg배린선알（CTX），후경복강주사건강인외주혈단개핵세포（PBMC）동시배부피하접충인삼음유선암세포MDA-MB-231；단순면역조지주사CTX급PBMC；단순하류조지접충MDA-MB-231；공백대조조불작임하처리。정기관찰각조소서생물학급면역학특정。결과면역하류조성류잠복기（10~12 d）교단순하류조（8~10 d）연장，종류생장속도감완，제5주말종류체적분별위1244.82±792.82 mm3화4308.77 mm3（P<0.01），생존솔제고（P<0.01）。접수면역중건적소서외주혈인IgG우제2주즉가측도，병축점상승，교미접수면역중건소서차이유통계학의의（P<0.01）。외주혈중CD3+세포비례우제2주축점하강，단우제9주잉가측도。제9주소서비장세포중CD3+T세포비례고체55.3%（면역하류조）급52.7%（단순하류조）。면역하류조소서비지수9.64 mg/g명현고우단순면역조3.82±0.31 mg/g급공백대조조1.51±0.14 mg/g。결론성공구건은정적구유인면역학특정적NOD/SCID소서모형，병관찰도기대삼음유선암산생면역응답，가위삼음유선암면역치료연구제공교위이상적동물모형。
Objective To establish a NOD/SCID mouse model with human immune reconstitution and observe its immune response to human triple-negative breast cancer xenograft. Methods Twenty-four NOD/SCID mice without immune leakage were subjected to cyclophosphamide (CTX) treatment 3 days prior to immune reconstitution with human peripheral blood mononuclear cell (PBMC) injection and subcutaneous transplantation of human triple-negative breast cancer MDA-MB-231 cells, CTX treatment and PBMC injection without tumor cell transplantation, MDA-MB-231 cell transplantation only, or no treatments. The tumor growth and immune responses of the mice were observed at regular intervals. Results Compared with the tumor-bearing mice, the tumor-bearing mice with immune reconstitution showed prolonged incubation period of tumor formation, slower tumor growth rate and increased survival rate. Human IgG and CD3+T cells were detected in the peripheral blood of the mice 1 week after human PBMC injection. The percentage of CD3+T cells in the spleen cells was 55.3%at 9 weeks in tumor-bearing mice with immune reconstitution and 52.7% in tumor-bearing mice without immune reconstitution. The spleen index of the tumor-bearing mice with immune reconstitution was much higher than that in mice with only immune reconstitution and the control mice (9.64 vs 3.82±0.31 and 1.51±0.14 mg/g). Conclusion A stable NOD/SCID mouse model with immune reconstitution has been established successfully, which shows immune responses to triple-negative breast cancer xenografts and allows studies of immunological therapy study of triple-negative breast cancer.