Major Vault Protein in Macrophages Reprograms Immune Microenvironment and Inhibits Occurrence and Development of Liver Cancer
10.3971/j.issn.1000-8578.2025.24.0784
- VernacularTitle: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
- Author:
Shimeng ZHOU
1
;
Mengmeng LI
1
;
Shouyu WANG
1
Author Information
1. Medical School of Nanjing University, Nanjing 210008, China.
- Publication Type:BASICRESEARCH
- Keywords:
Major vault protein;
Liver cancer;
Tumor microenvironment;
Macrophage;
CD8+ T cell
- From:
Cancer Research on Prevention and Treatment
2025;52(2):118-126
- CountryChina
- Language:Chinese
-
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.
