Better pancreatic adenocarcinoma outcomes linked to anti-EBV TCR CDR3 detection via tumor RNAseq files

Although the Epstein-Barr virus (EBV) is implicated in several cancer types, its potential role in the initiation and progression of pancreatic cancer remains poorly understood. In this study, T-cell receptor (TCR) complementarity-determining region 3 (CDR3s) were isolated from tumor-derived RNAseq files of two independent pancreatic adenocarcinoma datasets. Patients found to have exact matches to anti-EBV TCR CDR3s exhibited better overall and disease-free survival across both datasets. For example, for one dataset: 91 cases positive for anti-EBV TCR CDR3s had a median overall survival (OS) of 22.27 months versus 43 cases negative for anti-EBV CDR3s, with a median OS of 14.95 months (logrank p-value = 0.0195). Expression of immune marker genes representing T-cell functions were significantly higher in cases with anti-EBV TCR CDR3s, consistent with a potential role for enhanced anti-viral immune activity in these patients. These findings also suggest that several immune marker genes studied in this report could serve as novel biomarkers for pancreatic adenocarcinoma and may hold clinical value for prognoses. Additionally, genomic anomaly assessments revealed that anti-EBV CDR3-positive samples had significantly lower mutation counts, consistent with a greater role for EBV in supporting the development of pancreatic adenocarcinoma than previously recognized. The findings justify consideration of assessments of EBV status and tumor mutation burdens for patient stratification. Also, EBV-targeted immunotherapy for pancreatic adenocarcinoma may be considered for clinical trials.