Zhang Qiao-Chu, Li Xi, Liu Rui-Lei, Jiang Hua, Huang Ze-Nan, Liu Yu, Tang Mi, Huang Yong
Department of Thyroid and Breast Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2015 Jan;35(1):56-61.
To establish a NOD/SCID mouse model with human immune reconstitution and observe its immune response to human triple-negative breast cancer xenograft.
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.
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).
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.
建立具有人免疫重建的NOD/SCID小鼠模型，并观察其对人三阴性乳腺癌异种移植的免疫反应。
24只无免疫渗漏的NOD/SCID小鼠，在用人外周血单个核细胞（PBMC）注射进行免疫重建和皮下移植人三阴性乳腺癌MDA-MB-231细胞前3天接受环磷酰胺（CTX）治疗，或仅接受CTX治疗和PBMC注射而不进行肿瘤细胞移植，或仅进行MDA-MB-231细胞移植，或不进行任何处理。定期观察小鼠的肿瘤生长和免疫反应。
与荷瘤小鼠相比，具有免疫重建的荷瘤小鼠肿瘤形成潜伏期延长，肿瘤生长速度减慢，生存率提高。在注射人PBMC后1周，小鼠外周血中检测到人IgG和CD3(+) T细胞。具有免疫重建的荷瘤小鼠在9周时脾细胞中CD3(+) T细胞百分比为55.3%，无免疫重建的荷瘤小鼠为52.7%。具有免疫重建的荷瘤小鼠的脾指数远高于仅进行免疫重建的小鼠和对照小鼠（9.64对3.82±0.31和1.51±0.14 mg/g）。
成功建立了具有免疫重建的稳定NOD/SCID小鼠模型，该模型对三阴性乳腺癌异种移植表现出免疫反应，可用于三阴性乳腺癌免疫治疗研究。
