SLC5A11 Mediates Metformin-Induced PD-L1 Suppression to Enhance Cancer Immunotherapy through AMPK-IRF1 Signaling - PubMed
8 days ago
- #Metformin
- #PD-L1
- #Cancer Immunotherapy
- SLC5A11 identified as a key mediator of metformin sensitivity in cancer treatment through CRISPR screening.
- Metformin binds directly to SLC5A11 at specific residues (Asn78 and Glu102), suppressing PD-L1 expression via AMPK-IRF1 signaling.
- SLC5A11 knockout eliminates metformin's effects, while its reconstitution restores responsiveness, confirming its critical role.
- Combining metformin with anti-PD1 therapy enhances T cell infiltration and antitumor effects in lung and pancreatic cancer models.
- Metformin pretreatment boosts PBMC-mediated cytotoxicity against tumor cells and patient-derived organoids in ex vivo studies.
- The study suggests a novel SLC5A11-AMPK-PD-L1 axis, supporting metformin's combination with checkpoint inhibitors in immunotherapy.