Establishment of a humanized tumor-immune microenvironment mouse model
10.3781/j.issn.1000-7431.2024.2407-0459
- VernacularTitle:人源化肿瘤-免疫微环境小鼠模型的建立
- Author:
Haifeng CHEN
1
;
Yizong DING
;
Junlin ZHU
;
Qian CHEN
;
Yujie FU
;
Jun DENG
Author Information
1. 上海交通大学医学院附属仁济医院上海市肿瘤研究所,上海 200032
- Publication Type:Journal Article
- Keywords:
Human peripheral blood mononuclear cells;
Humanized mice;
Patient-derived xenografts;
Tumor-immune microenvironment
- From:
Tumor
2024;44(8):821-831
- CountryChina
- Language:Chinese
-
Abstract:
Objective:This study aims to construct a human peripheral blood mononuclear cell(PBMC)-NPSG-PDX(patient-derived xenograft)model,by transferring PBMCs into NPSG(NOD-PrkdcscidIl2rgnull/Shjh)mice and transplanting human tumor tissues.This model mimics the human tumor microenvironment to investigate the interactions between tumors and the immune system.Methods:PBMCs from healthy donors were transferred to NPSG mice to generate hPBMC-NPSG model.Patient-derived xenografts(PDX)were established in nude(BALB/c-nu)mice.Third-generation PDX tumors were then transplanted into hPBMC-NPSG mice to establish the hPBMC-NPSG-PDX model.Mouse body weight was monitored,and flow cytometry was used to analyze immune reconstitution and T cell function.Tumor growth was evaluated,and immunohistochemistry was performed to analyze tumor morphology and immune cell infiltration.Results:Fourteen days after constructing the hPBMC-NPSG mouse model,the proportion of human hu-CD45+CD3+T cells reached 97％.The proportions of human CD8+T,CD4+T,CD56+natural killer(NK),and CD19+B cells were 64％,24％,4.6％,and 1.0％,respectively.Human CD4+and CD8+cells secreted various cytokines(IL-2,IFN-γ,and TNF-α)and expressed cytotoxic molecules(FasL,granzyme B,and perforin)28 days post reconstitution.Tumor growth in hPBMC-NPSG-PDX mice was rapid initially but then stabilized.Immunohistochemistry staining revealed typical tumor morphology,and tumor cell apoptosis was observed in areas with immune cell infiltration.Conclusion:This study successfully constructed a hPBMC-NPSG-PDX model that effectively simulates the human tumor microenvironment,providing an ideal platform for tumor immunology research.
