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Tumor immune microenvironment delineates progression trajectories of distinct nasopharyngeal carcinoma phenotypes

Title: Tumor immune microenvironment delineates progression trajectories of distinct nasopharyngeal carcinoma phenotypes
Authors: Eugenia Li Ling Yeo; Boon Hao Hong; Shi Hui Tay; Jialing Neo; Enya Hui Wen Ong; Wen Min Chow; Kah Min Tan; Kar Perng Low; Adelene Yen Ling Sim; Tianzhu Lu; Xin Zhang; Luo Huang; Janice Ser Huey Tan; Joseph Tien Seng Wee; Yoke Lim Soong; Kam Weng Fong; Terence Wee Kiat Tan; Sze Yarn Sin; Xin Xiu Sam; Jacqueline Siok Gek Hwang; Tony Kiat Hon Lim; Jia-Ying Joey Lee; Lit-Hsin Loo; Khee Chee Soo; Narayanan Gopalakrishna Iyer; Kwok Seng Loh; Joshua K. Tay; Jianjun Liu; Mei Kim Ang; Joe Poh Sheng Yeong; Jin Xin Bei; Sze Huey Tan; Darren Wan Teck Lim; Melvin Lee Kiang Chua
Source: Cell Reports Medicine, Vol 6, Iss 6, Pp 102143- (2025)
Publisher Information: Elsevier
Publication Year: 2025
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: nasopharyngeal carcinoma; ascending; descending; genomics; tumor immune microenvironment; Medicine (General); R5-920
Description: Summary: We investigate the molecular landscape of locally advanced nasopharyngeal carcinoma (LA-NPC) subtypes: limited (L), ascending (A), descending (D), and ascending-descending (AD). Using a cohort of 994 patients, we perform germline and somatic whole-exome sequencing (WES), transcriptomic profiling, multiplex immunohistochemistry (mIHC), and spatial histopathological analyses of tumor whole-slide images (WSIs). Germline WES reveals the most variants in AD subtypes, but somatic WES shows no subtype-specific mutations. Transcriptomics reveals higher extracellular matrix (ECM) gene expression in A and AD subtypes and higher immune gene expression in D and AD subtypes, agreeing with deconvolution and mIHC. Tumor immune microenvironment (TIME) of node-negative (N0) and node-positive (N+) L subtypes, considered early nasopharyngeal carcinoma (NPC), resembles A and D subtypes, respectively, suggesting distinct evolutionary trajectories. Spatial WSI analyses identify the most immune-dense tumors among D subtypes and association of TIME with disease-free survival in AD subtypes. These findings highlight the TIME’s role in LA-NPC progression and its potential impact on treatment strategies.
Document Type: article in journal/newspaper
Language: English
Relation: http://www.sciencedirect.com/science/article/pii/S2666379125002162; https://doaj.org/toc/2666-3791; https://doaj.org/article/22af45ed79d44675be2a5ee46cd0f83d
DOI: 10.1016/j.xcrm.2025.102143
Availability: https://doi.org/10.1016/j.xcrm.2025.102143; https://doaj.org/article/22af45ed79d44675be2a5ee46cd0f83d
Accession Number: edsbas.756DCCE0
Database: BASE