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

作者：Zheng-Yu Qian, Yuqing Deng, M. Xi, X M Zhang, Hui Sun, Minjie Mao, Xiao-Jing Luo, Mengmeng Li, Qihua Zhang, B. Chen, Yi‐Qian Pan, Jia Liu, Ming-Ming He, Haojie Chen, Chiu-Wing Yeung, Zheng Yashang, Jiajia Huang, Meng Yang, Zong-Jian Li, Zhao-Lei Zeng, Huai‐Qiang Ju, Rui-Hua Xu, Hui Luo · 发表于：Cancer Discovery · 年份：2026 · DOI：10.1158/2159-8290.cd-25-1449 · 被引用次数：1 · 研究领域：Metabolomics and Mass Spectrometry Studies、Ferroptosis and cancer prognosis、Gut microbiota and health

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 3 independent cohorts of 288 samples, we established an integrated risk assessment framework spanning the entire therapeutic continuum: (i) a baseline predictor for initial responders based on metabolite signatures; (ii) an on-treatment predictor in prognosticating long-term responders among initial ones based on treatment-induced metabolic shift patterns; and (iii) a real-time model based on dual alteration of sphingolipid and glycerophospholipid dynamically stratifying progression risk. Meanwhile, 2 dietary metabolites, garlic-derived S-allyl-L-cysteine and cruciferous vegetable-derived indole-3-carbinol, were confirmed to improve outcomes by promoting NK-cell infiltration and reversing CD8+ T-cell exhaustion. In conclusion, we provide the first metabolomic roadmap for precision chemoimmunotherapy in ESCC, unifying baseline prediction, longitudinal surveillance, and dietary modulation into a clinically actionable paradigm. SIGNIFICANCE: We established a large-scale plasma metabolomic database from patients with ESCC undergoing chemoimmunotherapy, defining the first noninvasive, comprehensive, and precise monitoring framework for treatment response prediction...