中国病理生理杂志2026，Vol.42Issue(4)：759-766,8.DOI:10.3969/j.issn.1000-4718.2026.04.014
敲除MAST4通过调控AKT/FOXO3信号通路延缓CD8+T细胞耗竭
Knockout of MAST4 attenuates CD8+T-cell exhaustion by modulating AKT/FOXO3 signaling pathway
摘要
Abstract
AIM:Based on single-cell transcriptomic data from esophageal cancer,this study aims to eluci-date the expression pattern and molecular mechanisms involving which microtuble-associated serine/threonine kinase fami-ly member 4(MAST4)regulates CD8+T-cell functional exhaustion,thus providing a theoretical basis for identifying thera-peutic targets for the intervention of CD8⁺ T-cell exhaustion.METHODS:Based on the single-cell transcriptomic dataset(GSE160269)from patients with esophageal carcinoma,Seurat 5.0.2 was used for data quality control,normalization,and immune cell subcluster annotation to characterize the molecular signatures of exhausted CD8+T cells and evaluate the expression patterns of MAST4 within this subpopulation.The MAST4 expression in exhausted CD8+T cell subpopulation was validated by RT-qPCR.Functional exhaustion and cytokine secretion of CD8+T cells were assessed by flow cytome-try.MAST4-knockout CD8+T cells were generated using CRISPR/Cas9,and phosphorylation levels of AKT and FOXO3 were measured by Western blot.RESULTS:Bioinformatics analyses revealed selective overexpression of the protein ki-nase MAST4 in terminally exhausted CD8+T cells,with significant positive correlations between MAST4 expression and in-hibitory receptors such as PD-1 and TIM-3.CRISPR/Cas9-mediated knockout of MAST4 significantly reduced functional exhaustion in murine CD8+T cells and was accompanied by markedly increased phosphorylation of AKT and FOXO3(P<0.05).CONCLUSION:Knockout of MAST4 delays terminal exhaustion differentiation of CD8+T cells,possibly through modulation of the AKT/FOXO3 signaling pathway.关键词
食管癌/微管相关丝氨酸/苏氨酸激酶家族成员4/CD8+T细胞耗竭/AKT/FOXO3信号通路Key words
esophageal carcinoma/microtubule-associated serine/threonine kinase family member 4/CD8+T-cell exhaustion/AKT/FOXO3 signaling pathway分类
医药卫生引用本文复制引用
冯贤珍,刘宇,王佳,鞠振宇,吕明..敲除MAST4通过调控AKT/FOXO3信号通路延缓CD8+T细胞耗竭[J].中国病理生理杂志,2026,42(4):759-766,8.基金项目
长治医学院博士科研启动基金项目(No.2024BS18) （No.2024BS18）
山西省高等学校科技创新项目(No.2023L202) （No.2023L202）
再生医学教育部重点实验室(暨南大学)开放基金项目(No.ZSYXM202405) （暨南大学）
