{"id":3214,"date":"2025-11-19T02:08:47","date_gmt":"2025-11-19T02:08:47","guid":{"rendered":"https:\/\/medicine.nus.edu.sg\/medphc\/?p=3214"},"modified":"2025-11-19T02:08:47","modified_gmt":"2025-11-19T02:08:47","slug":"fungal-microbiota-signatures-anticipate-neoadjuvant-immunochemotherapy-outcomes-in-esophageal-cancer","status":"publish","type":"post","link":"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/fungal-microbiota-signatures-anticipate-neoadjuvant-immunochemotherapy-outcomes-in-esophageal-cancer\/","title":{"rendered":"Fungal microbiota signatures anticipate neoadjuvant immunochemotherapy outcomes in esophageal cancer"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-3215\" src=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/11\/20251008-GS-300x169.jpg\" alt=\"\" width=\"950\" height=\"535\" srcset=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/11\/20251008-GS-300x169.jpg 300w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/11\/20251008-GS-1024x576.jpg 1024w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/11\/20251008-GS-768x432.jpg 768w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2025\/11\/20251008-GS.jpg 1280w\" sizes=\"auto, (max-width: 950px) 100vw, 950px\" \/><\/p>\n<h2>Abstract<\/h2>\n<div id=\"sec-1\" class=\"subsection\">\n<p id=\"p-2\"><strong>Background<\/strong> Predicting neoadjuvant immunochemotherapy (NICT) response remains a critical challenge in esophageal squamous cell carcinoma (ESCC) management. While the gut bacteriome\u2019s role in immunotherapy has been established, the mycobiome\u2019s 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.<\/p>\n<\/div>\n<div id=\"sec-2\" class=\"subsection\">\n<p id=\"p-3\"><strong>Methods<\/strong> 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 <em>Candida_boidinii<\/em> in syngeneic mouse experiments with anti-programmed cell death protein-1 (PD-1) therapy.<\/p>\n<\/div>\n<div id=\"sec-3\" class=\"subsection\">\n<p id=\"p-4\"><strong>Results<\/strong> Patients with ESCC exhibited significant mycobiome dysbiosis compared with healthy controls, characterized by reduced alpha diversity and enrichment of pathogenic fungi including <em>s_Rhodotorula_minuta<\/em>, <em>s_Actinomucor_elegans<\/em>, and <em>s_Candida_zeylanoides<\/em>. 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 (<em>s_Candida_boidinii<\/em>, <em>g_Meyerozyma<\/em>, <em>s_Meyerozyma_guilliermondii<\/em>, <em>s_Trichosporon_dermatis<\/em>) that correlated with Th1-polarized immunity and elevated cytotoxic markers (interferon-\u03b3, interleukin (IL)-12p70, IL-2). Non-responders harbored immunosuppressive fungi (<em>s_Candida_albicans<\/em>, <em>s_Candida_parapsilosis<\/em>, <em>s_Candida_glabrata<\/em>, <em>g_Saccharomyces<\/em>) associated with Th2 skewing and regulatory cytokines (IL-4, IL-10, IL-13). Functional analysis revealed responders exhibited enhanced catabolic pathways and phospholipase activities, while non-responders showed upregulated nucleotide biosynthesis. The MLP model achieved robust discriminative performance (genus-level: training area under the receiver operating characteristic curve (AUC) 98.0%, test AUC 82.9%; species-level: training AUC 87.1%, test AUC 87.4%). <em>Candida_boidinii<\/em> administration enhanced anti-PD-1 efficacy in mice, validating predicted metabolomic and immune changes.<\/p>\n<\/div>\n<div id=\"sec-4\" class=\"subsection\">\n<p id=\"p-5\"><strong>Conclusions<\/strong> Baseline gut mycobiome signatures predict NICT response in ESCC with high accuracy. Experimental validation confirms functional causality, enabling precision medicine approaches for patient stratification and identifying therapeutic targets.<\/p>\n<p>Full Article:\u00a0<a href=\"https:\/\/jitc.bmj.com\/content\/13\/10\/e011508\">https:\/\/jitc.bmj.com\/content\/13\/10\/e011508<\/a><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Abstract Background Predicting neoadjuvant immunochemotherapy (NICT) response remains a critical challenge in esophageal squamous cell carcinoma (ESCC) management. While the gut bacteriome\u2019s role in immunotherapy has been established, the mycobiome\u2019s 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. [&hellip;]<\/p>\n","protected":false},"author":9345,"featured_media":3215,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[5],"tags":[],"class_list":["post-3214","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.4 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Fungal microbiota signatures anticipate neoadjuvant immunochemotherapy outcomes in esophageal cancer - Pharmacology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/fungal-microbiota-signatures-anticipate-neoadjuvant-immunochemotherapy-outcomes-in-esophageal-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Fungal microbiota signatures anticipate neoadjuvant immunochemotherapy outcomes in esophageal cancer - Pharmacology\" \/>\n<meta property=\"og:description\" content=\"Abstract Background Predicting neoadjuvant immunochemotherapy (NICT) response remains a critical challenge in esophageal squamous cell carcinoma (ESCC) management. While the gut bacteriome\u2019s role in immunotherapy has been established, the mycobiome\u2019s 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. 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