Longitudinal Plasma Metabolomics Guides Dynamic Risk Assessment and Dietary Modulation for Esophageal Squamous Cell...

Area of Science:

• Oncology
• Metabolomics
• Immunotherapy

Background:

• Esophageal squamous cell carcinoma (ESCC) shows varied responses to chemoimmunotherapy.
• Durable benefit is limited, requiring precise monitoring strategies.
• Current monitoring lacks dynamic assessment throughout treatment.

Purpose of the Study:

• To develop an integrated metabolomic framework for precision chemoimmunotherapy in ESCC.
• To establish predictors for initial response, long-term outcomes, and progression risk.
• To investigate the role of specific dietary metabolites in modulating treatment efficacy.

Main Methods:

• Longitudinal plasma metabolomics analysis of 541 samples from 252 ESCC patients in the ESCORT-1st trial.
• Analysis of three independent cohorts (288 samples) for validation.
• Development of predictive models for treatment response and progression risk.

Main Results:

• A baseline predictor for initial responders was identified using metabolite signatures.
• An on-treatment predictor was developed based on metabolic shifts to identify long-term responders.
• A real-time model using sphingolipid and glycerophospholipid alterations stratified progression risk.
• Dietary metabolites S-allyl-L-cysteine and indole-3-carbinol improved outcomes by enhancing NK cell infiltration and reversing CD8+ T cell exhaustion.

Conclusions:

• The study provides the first metabolomic roadmap for precision chemoimmunotherapy in ESCC.
• The framework integrates baseline prediction, longitudinal surveillance, and dietary modulation.
• This approach offers a clinically actionable paradigm for personalized ESCC treatment.