Cancer cellJournal Article
06 May 2025
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 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.
Declaration of interests M.X., Y.-X.Z., G.L., S.Z., Y.W., and Q.F. have filed a patent application related to the NPC-enriched TCRβs identified in this study for early detection, risk prediction, and immunotherapy of NPC. The patent is currently pending.
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