Immunosequencing identifies signatures of T cell responses for early detection of nasopharyngeal carcinoma.

Summary

By profiling peripheral blood TCRβ repertoires across NPC patients, EBV-seropositive at-risk controls, and seronegative controls, the authors derive a 208-CDR3β TCR signature (T-score) that accurately detects NPC and signals imminent diagnosis among at-risk individuals. NPC-enriched TCRs recognize both EBV and non-EBV tumor antigens, broadening diagnostic scope.

Key Findings

• A 208-CDR3β TCR signature (T-score) accurately diagnosed NPC in development and independent validation cohorts.
• Higher T-scores correlated with shorter time to clinical NPC diagnosis among EBV-seropositive at-risk individuals, enabling preclinical detection.
• NPC-enriched TCRs recognized both EBV-specific and non-EBV antigens expressed by NPC cells.

Clinical Implications

If validated prospectively, TCR-based screening could complement EBV serology to identify EBV-seropositive individuals who warrant endoscopic or imaging evaluation before symptoms arise.

Limitations

• Prospective, population-level screening performance and cost-effectiveness were not evaluated.
• Temporal stability and batch effects of TCR signatures over time were not fully characterized.

Future Directions

Prospective longitudinal screening trials in EBV-endemic regions should evaluate TCR signature stability, thresholds, integration with EBV serology, and downstream diagnostic pathways.