NIPAL1 Drives a Metabolic-Epigenetic Feedback Loop to Promote Lactate-Mediated Immune Evasion in Esophageal Cancer - PubMed
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- #NIPAL1
- #histone lactylation
- #immune evasion
- NIPAL1 drives a metabolic-epigenetic feedback loop in esophageal squamous cell carcinoma (ESCC).
- NIPAL1 recruits HCK to phosphorylate LDHA at Y10, enhancing glycolysis and lactate production.
- Lactate accumulation promotes p300-mediated histone H3K18 lactylation (H3K18la), activating NIPAL1 expression.
- This loop promotes tumor growth and immune evasion by impairing CD8+ T cell function.
- Pharmacological inhibition of HCK or p300 disrupts the loop and restores antitumor immunity.
- NIPAL1, p-LDHA (Y10), and H3K18la correlate with response to immune checkpoint blockade.
- Findings offer potential targets to improve immunotherapy efficacy in ESCC.