Immunosequencing identifies signatures of T cell responses for early detection of nasopharyngeal carcinoma
To identify nasopharyngeal carcinoma (NPC)-relevant T cell receptors (TCRs), we profile the repertoires of peripheral blood TCRβ chains from 228 NPC patients, 241 at-risk controls positive for serum Epstein-Barr virus (EBV) VCA-IgA antibody, and 251 seronegative controls. We develop a TCR-based signature (T-score) based on 208 NPC-enriched CDR3β sequences, which accurately diagnoses NPC in both the original and independent validation cohorts. Notably, a higher T-score, associated with a shorter time interval to NPC diagnosis, effectively identifies early-stage NPC among EBV-seropositive at-risk individuals prior to clinical diagnosis. These NPC-enriched TCRs react against not only EBV-specific antigens but also non-EBV antigens expressed by NPC cells, indicating a broad range of specificities. Moreover, the abundance of NPC-enriched CD8<sup>+</sup> T cells in blood correlates with the infiltration of non-exhausted T cell counterparts in tumors and predicts prolonged survival, suggesting that these NPC-enriched T cells have significant potential for disease monitoring and therapeutic applications.
Authors
- Guideng Li (ORCID: https://orcid.org/0000-0003-0840-7262)
- Su‐Mei Cao (ORCID: https://orcid.org/0000-0003-1749-517X)
- Weiwei Zhai (ORCID: https://orcid.org/0000-0001-7938-0226)
- Yanwen Zhou (ORCID: https://orcid.org/0000-0003-3636-0123)
- Haiwen Chen (ORCID: https://orcid.org/0000-0002-3836-9845)
- Mu‐Sheng Zeng (ORCID: https://orcid.org/0000-0003-3509-5591)
- Xinyu Zhang (ORCID: https://orcid.org/0000-0002-4986-4649)
- Zhonghua Liu (ORCID: https://orcid.org/0000-0003-3048-9823)
- Qisheng Feng
- Miao Xu (ORCID: https://orcid.org/0000-0001-7091-4199)
- Shanshan Zhang (ORCID: https://orcid.org/0000-0002-4170-7526)
- Yuqian Wang (ORCID: https://orcid.org/0000-0002-4543-8319)
- Yanhong Chen (ORCID: https://orcid.org/0000-0002-9550-6906)
- Xiang Zhou (ORCID: https://orcid.org/0000-0002-6908-683X)
- Xiao-Ping Ye
- Shang-Hang Xie
- Yi-Xin Zeng
Institutions
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Guangzhou Women and Children Medical Center (CN)
- Suzhou Institute of Systems Medicine (CN)
- Sun Yat-sen University Cancer Center (CN)
- State Key Laboratory of Respiratory Disease (CN)
- Institute of Zoology (CN)
- Columbia University (US)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Cancer Cell
- Published
- 2025-05-08
- DOI
- https://doi.org/10.1016/j.ccell.2025.04.009
- Citations
- 7
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 5.58