Gut microbiota-derived indole-3-lactic acid suppresses anti-PD-1 efficacy in esophageal squamous cell carcinoma - PubMed
5 hours ago
- #esophageal-cancer
- #immunotherapy-resistance
- #gut-microbiota
- Gut microbiota-derived indole-3-lactic acid (ILA) reduces anti-PD-1 immunotherapy efficacy in esophageal squamous cell carcinoma (ESCC).
- Ligilactobacillus salivarius (L. salivarius) is enriched in non-responders to immunotherapy and produces ILA, which suppresses tumor-infiltrating NKG7+CD8+ Tpex cells.
- ILA targets the aryl hydrocarbon receptor and downregulates NF-κB signaling in Tpex cells, impairing anti-tumor immunity.
- Pharmacological activation of NF-κB restores Tpex function and reverses immunotherapy resistance.
- Validation studies confirm the L. salivarius-ILA-NKG7+CD8+ Tpex axis as a resistance mechanism in ESCC patients.