HBV-associated hepatocellular carcinomas inhibit antitumor CD8⁺ T cell via the long noncoding RNA HDAC2-AS2.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Extracellular vesicles (EV) are critical mediators of intercellular communication within the tumor microenvironment, and cancer-cell-secreted EVs often facilitate cancer progression. Here we show that in HBV-associated HCC, tumor-cell-derived EVs contain a TGFβ-inducible long noncoding RNA, termed HDAC2-AS2. EVs enriched with HDAC2-AS2 facilitate cancer progression by suppressing cytotoxicity of intra-tumor CD8⁺ T cells. Mechanistically, in activated cytotoxic CD8⁺ T cells, translocation of the transcription factor cyclin-dependent kinase 9 (CDK9), to the cytoplasm is critical for functional integrity. HDAC2-AS2 targets and blocks cytosolic CDK9, and this results in exhaustion of PD-1

SUBMITTER: Gao Y 

PROVIDER: S-EPMC11871238 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature