Scholarlink

<p>The tumor microenvironment (TME) is a crucial mediator of tumor progression and treatment response. Here, we compare the immune microenvironments of HBV and non-HBV hepatocellular carcinoma (HCC) and investigate the reason for the persistence of HBV infection in the liver. We combine the Viral-Track method with scRNA sequencing and profile the transcriptomes of 70,056 cells from HBV and non-HBV-HCC patients. In addition to hepatocytes and macrophages, HBV transcripts were also detected in T and B cells using the Viral-Track method, confirming the lymphotropic nature of HBV in scRNA-sequencing data for the first time, to the best of our knowledge. HBV-HCC tumors have reduced levels of NK cells, macrophages, DCs, and increased malignant hepatocytes compared with those in non-HBV HCC. Notably, we report the enrichment of metallothioneins (MTs), particularly MT1G, in HBV-related HCC TAMs, which is associated with a worse prognosis. HBV-tumor-infiltrated CD8⁺ T cells exhibit a dysfunctional cytotoxic phenotype, characterized by upregulated MDK and CTLA4 expression and reduced IFN-γ production, unlike the non-HBV-HCC. Additionally, HBV-HCC exhibits immunosuppressive ligand-receptor interactions, whereas non-HBV-HCC exhibits antitumor ligand-receptor interactions. Our deeper understanding of the HBV-HCC ecosystem using Viral-Track integrated scRNA sequencing provides insights into immune evasion mechanisms and HBV lymphotropism associated with viral persistence.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Viral-Track integrated single-cell RNA-sequencing reveals HBV lymphotropism and immunosuppressive microenvironment in HBV-associated hepatocellular carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月9日

查看全文
  • Zhepeng Liu,
  • Wajeeha Naz,
  • Tanzeel Yousaf,
  • Junwei Sun,
  • Qijia Wu,
  • Mingxiong Guo,
  • Geng Tian,
  • Guihong Sun

摘要

The tumor microenvironment (TME) is a crucial mediator of tumor progression and treatment response. Here, we compare the immune microenvironments of HBV and non-HBV hepatocellular carcinoma (HCC) and investigate the reason for the persistence of HBV infection in the liver. We combine the Viral-Track method with scRNA sequencing and profile the transcriptomes of 70,056 cells from HBV and non-HBV-HCC patients. In addition to hepatocytes and macrophages, HBV transcripts were also detected in T and B cells using the Viral-Track method, confirming the lymphotropic nature of HBV in scRNA-sequencing data for the first time, to the best of our knowledge. HBV-HCC tumors have reduced levels of NK cells, macrophages, DCs, and increased malignant hepatocytes compared with those in non-HBV HCC. Notably, we report the enrichment of metallothioneins (MTs), particularly MT1G, in HBV-related HCC TAMs, which is associated with a worse prognosis. HBV-tumor-infiltrated CD8⁺ T cells exhibit a dysfunctional cytotoxic phenotype, characterized by upregulated MDK and CTLA4 expression and reduced IFN-γ production, unlike the non-HBV-HCC. Additionally, HBV-HCC exhibits immunosuppressive ligand-receptor interactions, whereas non-HBV-HCC exhibits antitumor ligand-receptor interactions. Our deeper understanding of the HBV-HCC ecosystem using Viral-Track integrated scRNA sequencing provides insights into immune evasion mechanisms and HBV lymphotropism associated with viral persistence.