The inhibitory effect of GSDME on tumor progression and its underlying mechanisms in mice
10.13431/j.cnki.immunol.j.20240003
- VernacularTitle:小鼠GSDME对肿瘤进展的抑制作用及其机制
- Author:
Degao CHEN
1
;
Renren YU
;
Yucui WU
;
Yangping BIAN
;
Hao LYU
;
Ting YUAN
;
Bo ZHU
Author Information
1. 400037,陆军军医大学新桥医院肿瘤科肿瘤免疫治疗重庆市重点实验室
- Keywords:
GSDME;
CD8+T cell;
Macrophage;
Dendritic cell;
Caspase-3
- From:
Immunological Journal
2024;40(1):19-25
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to explore the role of mouse GSDME in tumor progression and its mechanisms.Wide type and GSDME knockout mice were used to establish tumor models and the tumor growth was monitored;CRISPR-Cas9 was employed to knockout GSDME in MC38 cells.Bone marrow-derived macrophage and dendritic cells were culture in vitro and adoptively transferred into tumor-bearing mice,respectively.Western blotting was conducted to detect protein expression in cells;flow cytometry was used to analysis the immune cell number,CD8+T cell function,and Cleaved Caspase-3 expression in TAM and TADC cells.According to the above experiments,we found that GSDME deficiency promoted tumor progression in mice.GSDME knockout reduced the number of CD8+T cells and decreased IFN-γ and Perforin in CD8+T cells in tumors.GSDME was mainly expressed in macrophages and dendritic cells,and adoptive transferring GSDME deficient macrophages or dendritic cells did not affect tumor progression.However,GSDME deficient mice reduced the ratio of Cleaved Caspase-3 positive macrophages and dendritic cells in tumors,and Cleaved Caspase-3 positive macrophages expressed more iNOS and MHCII,while Cleaved Caspase-3 positive dendritic cells expressed more CD80 and CD86.In general,GSDME increases Cleaved Caspase-3 positive macrophages and dendritic cells that promote CD8+T cell function,thereby inhibiting tumor progression.
