Tumor immune microenvironment delineates progression trajectories of distinct nasopharyngeal carcinoma phenotypes
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.
Authors
- Xin Xiu Sam (ORCID: https://orcid.org/0000-0003-0583-2319)
- Joseph Wee (ORCID: https://orcid.org/0000-0001-6123-1257)
- Enya H.W. Ong (ORCID: https://orcid.org/0000-0002-2591-7910)
- N. Gopalakrishna Iyer (ORCID: https://orcid.org/0000-0002-8812-6219)
- Tianzhu Lu (ORCID: https://orcid.org/0000-0002-1524-7909)
- Yoke Lim Soong (ORCID: https://orcid.org/0000-0003-3677-8669)
- Tony Kiat Hon Lim (ORCID: https://orcid.org/0000-0003-0645-5164)
- Mei‐Kim Ang (ORCID: https://orcid.org/0000-0003-3209-864X)
- Xin Zhang (ORCID: https://orcid.org/0000-0001-9422-3499)
- Kwok Seng Loh (ORCID: https://orcid.org/0000-0002-6324-1691)
- Sze Huey Tan (ORCID: https://orcid.org/0000-0002-3089-7379)
- Jia-Ying Joey Lee (ORCID: https://orcid.org/0000-0002-0420-7098)
- Eugenia L.L. Yeo (ORCID: https://orcid.org/0000-0002-3639-7404)
- Wan‐Teck Lim (ORCID: https://orcid.org/0000-0002-4655-0206)
- Jialing Neo (ORCID: https://orcid.org/0009-0002-9921-8095)
- Adelene Yen Ling Sim
- Lit‐Hsin Loo (ORCID: https://orcid.org/0000-0001-6303-9840)
- Khee Chee Soo (ORCID: https://orcid.org/0000-0001-8768-6786)
- Boon Hao Hong (ORCID: https://orcid.org/0000-0002-2822-7480)
- Joshua K. Tay (ORCID: https://orcid.org/0000-0001-5653-4659)
- Melvin L.K. Chua (ORCID: https://orcid.org/0000-0002-1648-1473)
- Kah Min Tan (ORCID: https://orcid.org/0009-0000-7535-8734)
- Kam Weng Fong (ORCID: https://orcid.org/0000-0001-9745-3687)
- Shi Hui Tay
- Jianjun Liu (ORCID: https://orcid.org/0000-0002-0288-647X)
- Janice Ser Huey Tan (ORCID: https://orcid.org/0000-0002-7011-2740)
- Luo Huang
- Joe Poh-Sheng Yeong (ORCID: https://orcid.org/0000-0002-6674-7153)
- Kar Perng Low
- Jin Bei
- Jacqueline Siok Gek Hwang
- Terence Wee Kiat Tan
- Sze Yarn Sin
- Wen Min Chow
Institutions
- Singapore General Hospital (SG)
- Jiangxi Provincial Cancer Hospital (CN)
- National Cancer Centre Singapore (SG)
- Chongqing Cancer Hospital (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-05-23
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102143
- Citations
- 2
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 1.87