HERV-K TM Subunit Elicits CD8⁺ T Cell Anergy and Tumor Immune Evasion via Targeting CD3 Coreceptor ε in AML and PDAC.

ABSTRACT: CD8⁺ T cell anergy is a critical driver of cancer immune evasion, but the underlying causes and mechanisms remain elusive. Here, the functional human endogenous retroviruses-K envelope (HERV-K Env) subunit transmembrane (K-TM) is identified as a potent viral immune checkpoint that induces CD8⁺ T cell anergy and elicits immune evasion in acute myeloid leukemia (AML) and pancreatic duct adenocarcinoma (PDAC). K-TM subunits are highly expressed in CD8⁺ T cells and enriched in sera of cancer patients. K-TM-low CD8⁺ T cells show potent tumor-killing ability, whereas K-TM-high CD8⁺ T cells are incapable of eliciting anti-tumor effects. Both intracellular and extracellular K-TM inhibit CD8⁺ T cell activation and cytokine release, l

SUBMITTER: Li M 

PROVIDER: S-EPMC12767058 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature