HERV‐K TM Subunit Elicits CD8 ⁺ T Cell Anergy and Tumor Immune Evasion via Targeting CD3 Coreceptor ε in AML and PDAC (Adv. Sci. 1/2026)

Immune Therapies In their Research Article (DOI: 10.1002/advs.202417432), Rongzhen Xu, Qi Zhang, Mengyuan Li, and co-workers identify the human endogenous retrovirus-K envelope transmembrane subunit (K-TM) as a novel viral immune checkpoint that drives CD8+ T cell anergy and promotes immune evasion in acute myeloid leukemia and pancreatic ductal adenocarcinoma. K-TM binds directly to the CD3ε ITAM domain, suppresses TCR signaling, and impairs antitumor immunity. Targeting K-TM reverses T cell dysfunction and inhibits tumor growth, revealing a conceptually new target for immune therapies.