Abstract C032: Comparison of genomic drivers and transcriptomic features of immunogenicity in pancreatic malignancies

Abstract Pancreatic neuroendocrine tumors (pNETs) have variable clinical behavior and nearly 40% of patients are diagnosed with advanced disease where there is a role for systemic treatments. A better understanding of the immunogenicity of pNETs will help discern if immunotherapy can be sequenced in the management of pNETs. In this study, we are characterizing the genomic and transcriptional landscape of pNETs (n=42, with 30 included in these preliminary analyses) vs. pancreatic ductal adenocarcinomas (PDAC, n=81). Whole genome and transcriptome sequencing (WGTS) and clinical data are analyzed using R-based bioinformatics tools (i.e., DriverNet for driver-gene prediction and maftools for mutation visualization and analyses). Tumor mutational burden (TMB) is calculated, and mutation patterns are visualized through oncoplots incorporating clinical data. We are also evaluating a four-chemokine (c-Score, CCL4, CCL5, CXCL9, CXCL10) inflammatory signature, which we have shown to correlate with immunogenicity and response to immune checkpoint blockade across multiple cancer types. Circos plots are generated to integrate single-nucleotide variants, indels, copy number alterations, and chromosomal rearrangements into a single cohesive view of genomic instability. In our preliminary assessment of 30/42 pNET cases, DriverNet analysis identified expected driver differences between pNETs and PDACs. pNETs displayed a distinct spectrum of mutations with a lower TMB and c-Score relative to PDAC (no data here, would be nice to give a some sort of statistical comparison). TCR repertoire would be good to add if you ave room/data. In summary, our preliminary data suggest that pNETs have lower immunogenicity compared to PDACs, but as with PDACs, there may be a subset of pNETs that may respond to immunotherapy treatments. Citation Format: James Vafiadis, Joan M. Romero, George Zogopoulos. Comparison of genomic drivers and transcriptomic features of immunogenicity in pancreatic malignancies [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr C032.