生物
免疫系统
细胞毒性T细胞
免疫监视
CTL公司*
MHC I级
癌症研究
抗原
胶质瘤
细胞生物学
免疫学
获得性免疫系统
Wnt信号通路
主要组织相容性复合体
干细胞
信号转导
CD8型
遗传学
体外
作者
Wei Yang,Yanyan Li,Ruoling Gao,Zenghe Xiu,Ting Sun
出处
期刊:Oncogene
[Springer Nature]
日期:2019-10-07
卷期号:39 (5): 1098-1111
被引量:77
标识
DOI:10.1038/s41388-019-1045-6
摘要
Glioma stem cells (GSCs) decrease T cells cognition and evade systemic immunosurveillance via downregulations or defects of major histocompatibility complex class I (MHC-I) molecule and antigen-processing machinery (APM) components. Improvement of tumor surface antigens of GSCs may be effective strategy to trigger an adaptive immune response and activate cytotoxic T cells (CTLs) to eliminate glioma. In this study, our data indicated that downregulations of MHC-I and APM components expressions were associated with Wnt pathway activation in GSCs. Histone deacetylases (HDAC) inhibition improved MHC-I and APM components expressions, which could be partly reverted by Wnt pathway activation. Blocking CTLs-mediated killing decreased the anti-tumor effect of tumor lysate vaccine. The enhancement of T cells immune response resulting from HDAC inhibition was dependent on CTLs cognition on tumor antigens presented by upregulated MHC-I molecule in GSCs. These data suggest that suppression of stemness pathway may be effective for GSCs-based immunotherapy against immune-escaped tumors.
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