MiR-340-5p regulates PD-L1 and predicts pembrolizumab response in extranodal NK/T-cell lymphoma

Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive, chemoresistant non-Hodgkin lymphoma subtype with poor patient outcomes linked to elevated PD-L1 expression. This study investigates miRNA-mediated regulation of PD-L1, focusing on miR-340-5p and miR-424-5p as novel therapeutic targets and predictive biomarkers for pembrolizumab response. Through miRNA sequencing and functional assays, miR-340-5p and miR-424-5p were identified as key modulators of PD-L1 in drug-resistant ENKTL cells, with their roles validated via ribonucleoprotein immunoprecipitation and luciferase reporter assays. Notably, elevated miR-340-5p levels in PD-L1-negative ENKTL tissues were inversely correlated with soluble PD-L1, implicating miR-340-5p in immune evasion mechanisms. Additionally, low serum levels of miR-340-5p were associated with reduced pembrolizumab efficacy, positioning miR-340-5p as a promising predictive biomarker for immune checkpoint blockade. These findings suggest that pre-treatment assessment of serum miR-340-5p could guide pembrolizumab therapy in ENKTL, optimizing treatment outcomes. Validation in larger cohorts is necessary to confirm the utility of miR-340-5p as a predictive biomarker for ENKTL immunotherapy.