肿瘤防治研究2025，Vol.52Issue(2)：118-126,9.DOI:10.3971/j.issn.1000-8578.2025.24.0784
巨噬细胞穹窿主体蛋白重塑免疫微环境抑制肝癌发生发展
Major Vault Protein in Macrophages Reprograms Immune Microenvironment and Inhibits Occurrence and Development of Liver Cancer
摘要
Abstract
Objective To explore the role and molecular mechanism of major vault protein(MVP)in tumor-associated macrophages in the occurrence and development of liver cancer.Methods The expression of MVP in macrophages was analyzed by bioinformatics method and multi-fluorescent immunohistochemical staining.Mice with MVP deficiency in macrophages were constructed by Cre/LoxP recombinant enzyme system.The proliferation and migration abilities of tumor cells were detected by cloning formation and Transwell migration assays.The effect of MVP in macrophages on tumorigenesis and development was investigated by mouse primary liver cancer model and subcutaneous tumor transplantation model.The effect of MVP on the tumor microenvironment was investigated by multi-fluorescent immunohistochemical staining.The effect of MVP on CD8+T cells was detected by cell co-culture,flow cytometry,qPCR,and ELISA.Results The high expression of MVP in tumor-associated macrophages.The downregulation of the expression of MVP in tumor-associated macrophages compared with para-carcinoma tissues.MVP deficiency in macrophages promoted the proliferation and migration of tumor cells(P<0.05),promoted the development of tumor in vivo(P<0.05),formed an immunosuppressive microenvironment and weakened CD8+T cell-mediated anti-tumor immunity(P<0.05).Conclusion MVP deficiency in macrophages can promote the occurrence and development of liver cancer by suppressing the function of CD8+T cells.关键词
穹窿主体蛋白/肝癌/肿瘤微环境/巨噬细胞/CD8+T细胞Key words
Major vault protein/Liver cancer/Tumor microenvironment/Macrophage/CD8+T cell分类
临床医学引用本文复制引用
周诗萌,李梦梦,王守宇..巨噬细胞穹窿主体蛋白重塑免疫微环境抑制肝癌发生发展[J].肿瘤防治研究,2025,52(2):118-126,9.基金项目
National Natural Science Foundation of China(No.82273157,82073114) 国家自然科学基金(82273157,82073114) （No.82273157,82073114）
