AK5 suppresses breast cancer progression and modulates anti-PD-L1 efficacy via the miR-182-5p/PD-L1 axis

Adenylate kinase 5 (AK5) is a poorly characterized metabolic enzyme with unknown roles in breast cancer. Single-cell transcriptomics revealed AK5 enrichment in malignant epithelial cells, and its low expression correlated with poor patient prognosis, suggesting tumor-suppressive functions. Functionally, AK5 overexpression inhibited, while its knockdown promoted, breast cancer cell proliferation, migration, and invasion. Mechanistically, AK5, dependent on its kinase activity, post-transcriptionally suppressed miR-182-5p maturation, thereby de-repressing -L1 expression. <i>In vivo</i> experiments have proved that AK5 overexpression attenuated tumor growth and synergized with anti-PD-L1 therapy. Our work defines AK5 as a novel tumor suppressor, unveils a kinase-dependent non-canonical role in regulating an immune checkpoint via miR-182-5p, and nominates it as a potential therapeutic target to sensitize tumors to immunotherapy.