TRNA-Derived Fragment tRF-22 Promotes Immunosuppression by Inhibiting HnRNPAB Ubiquitination in Esophageal Squamous Cell Carcinoma.

ABSTRACT: Small proportions of patients with esophageal squamous cell carcinoma (ESCC) benefit from immune checkpoint blockade therapy, making it urgent to identify factors that limit its effectiveness. It is found that tRF-22, a small RNA derived from tRNA^GlnCTG/TTG, promotes an immunosuppressive tumor microenvironment. High tRF-22 expression is associated with worse prognosis in ESCC. tRF-22 shapes immunosuppression by increasing polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) infiltration and suppressing CD8⁺ T cells. Mechanistically, it binds to Lys91 on hnRNPAB, inhibiting its ubiquitination by TRIM25, leading to the stabilization of hnRNPAB, which activates TGFB2 transcription. Accumulated TGFβ2 promotes MDSCs generation to drive immunosuppression in ESCC.

SUBMITTER: Pan L 

PROVIDER: S-EPMC12767015 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature