OBJECTIVETo establish a NOD/SCID mouse model with human immune reconstitution and observe its immune response to human triple-negative breast cancer xenograft.

METHODSTwenty-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.

RESULTSCompared 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).

CONCLUSIONA 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.