Epigenetic Silencing of RFX7 Defines a Transcriptional Axis Linking Lactate Metabolism to Immune Checkpoint Therapy in Glioblastoma - PubMed
2 hours ago
- #Epigenetics
- #Immunotherapy
- #Lactate Metabolism
- Epigenetic silencing of RFX7 via promoter hypermethylation reduces its expression in glioblastoma (GBM).
- Restoring RFX7 increases PIK3IP1 expression, inhibits PI3K/AKT signaling, and suppresses GBM progression.
- Loss of PIK3IP1 elevates lactate production and histone H4K12 lactylation (H4K12la), upregulating PD-L1/CSF1 and enhancing immunosuppression.
- Pharmacological lactate inhibition with Stiripentol reduces H4K12la, tumor growth, immunosuppressive cell infiltration, and improves response to immune checkpoint therapy.
- The RFX7-PIK3IP1 axis links lactate metabolism to immune suppression, offering a target for metabolic-immune modulation in GBM therapy.