肝细胞癌
病毒学
免疫
乙型肝炎病毒
获得性免疫系统
肝炎病毒
医学
病毒
免疫学
生物
癌症研究
免疫系统
作者
Liang Chen,Maojun You,Meijie Tian,Junliang Fu,Yanan Gao,Chunlin Wang,Zepeng Mu,Yang Li,Zhen Wang,Xueyi Teng,Zhenyu Zhu,Zhixian Hong,Jie Liang,Runsheng Chen,Fusheng Wang,Pengyuan Yang,Mark M. Davis
出处
期刊:Social Science Research Network
[Social Science Electronic Publishing]
日期:2020-01-01
摘要
In hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV+ HCC), the mechanisms by virus-derived antigens shape the T cell immune response remains unclear. Here, we employed bulk and single-cell multi-omics sequencing technologies to study the T cell receptor (TCR) repertoire, antigen specificity and epigenomic profiles in HBV+ HCC patients. We found that HBV is a major driver of T cells, with HBV-specific recurrent and expanding TCR clonotypes from CD8+ T cells, mucosal-associated invariant T (MAIT) cells and regulatory T cells (Tregs). HBV virions can directly activate MAIT cells in a MR1-dependent manner, indicating that these cells are not only sensors of metabolic products, but could participate directly in pathogen defense. And increased numbers of intratumoral Tregs, many of which are HBV specific, correlated with both increased viral titers and tumor size, while more a robust expansion of virus specific CD8+ T cells had better clinical prognosis after surgery. Integrating TCR and ATAC sequences also allowed us to track the epigenomic changes of specific T cell clonal lineages, with HBV-specific conventional CD8+ T cells expressing an effector phenotype when adjacent to the tumor, but cells of the same lineage exhibiting an “exhausted” phenotype in the tumor itself.
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