Knockout SQLE in melanoma cells potentiates anti-tumor immunity via improving CD8+T cell infiltration in tumor microenvironment
10.19405/j.cnki.issn1000-1492.2024.08.005
- VernacularTitle:SQLE敲除促进黑色素瘤肿瘤微环境CD8+T细胞浸润发挥抗肿瘤效应
- Author:
Yao DING
1
;
Wen LIU
;
Yiran LIAO
;
Shun LEI
;
Yan ZHANG
;
Yezi CHEN
;
Yi GONG
;
Qizhao HUANG
Author Information
1. 重庆大学附属肿瘤医院一期病房,重庆 400030
- Keywords:
squalene epoxidase;
melanoma;
tumor microenvironment;
tumor immunity
- From:
Acta Universitatis Medicinalis Anhui
2024;59(8):1315-1322
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of squalene epoxidase(SQLE)knockout in anti-tumor effect vial im-proving CD8+T cell infiltration in melanoma tumor microenvironment.Methods Both immunodeficient and immu-nocompetent mice were inoculated with SQLE knockout B16F10 cells to determine the cell-autonomous and non-au-tonomous regulation of malignancy.Antibody blockade,Luminex multiplex assays,and flow cytometry were em-ployed to explore the impact of SQLE gene knockout on the secretion of cytokines/chemokines and immune cell in-filtration.Bioinformatics analysis was conducted to validate the correlation between SQLE expression and immune infiltration as well as clinical prognosis in melanoma patients.Results Compared with immunodeficient mice,SQLE knockout significantly inhibited melanoma proliferation in immunocompetent mice and prolonged their surviv-al.SQLE knockout induced the secretion of cytokines and chemokines from tumor cells,improved CD8+T cell in-filtration in the tumor microenvironment,thereby potentiating anti-tumor immunity.Bioinformatics analysis sugges-ted a significant correlation between SQLE and its corresponding immune infiltration markers with the prognosis of melanoma patients.Conclusion SQLE regulates anti-tumor immunity by controlling cytokines and chemokines re-leasing in tumor microenvironment,thus holding promise as a novel tumor immunotherapy target and efficacy predic-tion molecular indicator.