Abstract Esophageal squamous cell carcinoma (ESCC) exhibits heterogeneous responses to chemoimmunotherapy, with only a minority achieving durable benefit, necessitating dynamic precision monitoring. Through longitudinal plasma metabolomics of 541 serial samples from 252 ESCORT-1st trial patients receiving chemoimmunotherapy plus three independent cohorts of 288 samples, we established an integrated risk assessment framework spanning the entire therapeutic continuum: (1) a baseline predictor for initial responders based on metabolite signatures; (2) an on-treatment predictor in prognosticating long-term responders among initial ones based on treatment-induced metabolic shift patterns; (3) a real-time model based on dual alteration of sphingolipid and glycerophospholipid dynamically stratifying progression risk. Meanwhile, two dietary metabolites, garlic-derived S-allyl-L-cysteine and cruciferous vegetable-derived indole-3-carbinol, were confirmed to improve outcomes by promoting NK cells infiltration and reversing CD8+ T cells exhaustion. In conclusion, we provide the first metabolomic roadmap for precision chemoimmunotherapy in ESCC, unifying baseline prediction, longitudinal surveillance, and dietary modulation into clinically actionable paradigm.
Qian et al. (Mon,) studied this question.