Fungal microbiota signatures anticipate neoadjuvant immunochemotherapy outcomes in esophageal cancer

作者：Liping Liang, Shijie Mai, Gautam Sethi, Yanyan Luo, Zeheng Ma, Lele Wu, Di Lu, Jimin Han, Ruijun Cai, Yongjian Zhou, Xinying Wang, Le Liu · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · DOI：10.1136/jitc-2025-011508 · 被引用次数：4 · 研究领域：Gut microbiota and health、Cancer Immunotherapy and Biomarkers、Cancer Research and Treatments

Background Predicting neoadjuvant immunochemotherapy (NICT) response remains a critical challenge in esophageal squamous cell carcinoma (ESCC) management. While the gut bacteriome’s role in immunotherapy has been established, the mycobiome’s predictive potential remains largely unexplored. This study investigated whether gut fungal signatures could serve as reliable biomarkers for NICT response prediction in patients with ESCC. Methods We performed internal transcribed spacer 2 sequencing on 155 fecal samples from 68 patients with ESCC (pre-NICT and post-NICT) and 19 healthy controls. Patients were stratified by tumor regression grade scores. We analyzed mycobiome-immune marker correlations and developed multilayer perceptron (MLP) models using Boruta feature selection. Performance was validated in 37 independent pretreatment patients. Functional causality was confirmed using Candida_boidinii in syngeneic mouse experiments with anti-programmed cell death protein-1 (PD-1) therapy. Results Patients with ESCC exhibited significant mycobiome dysbiosis compared with healthy controls, characterized by reduced alpha diversity and enrichment of pathogenic fungi including s_Rhodotorula_minuta , s_Actinomucor_elegans , and s_Candida_zeylanoides . Baseline mycobiome profiles distinguished treatment responders from non-responders before therapy initiation. Responders demonstrated higher fungal diversity, more stable co-occurrence networks, and enrichment of beneficial taxa ( s_Candida_bo...