32nd Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2017): Part One

Pancreatic adenocarcinoma (PDAC) is a lethal cancer with <7% of patients surviving past 5 years. T cell immunity has been linked to the exceptional outcome of the rare long-term survivors but the antigens are unknown. Methods To identify T cell antigens in long-term PDAC survivors, we assembled the largest cohorts of stage-matched short [n=68, median overall survival (OS) 0.8y] and long-term PDAC survivors (n=82, median OS 6y). To enable antigen discovery, we performed a combined analysis of whole exome sequencing, neoantigen prediction, T cell receptor (TCR) V-chain sequencing, 9-color multiplexed immunohis-tochemistry, and tumor transcriptomic profiling. To assess differential neoantigen immunogenicity, we performed neoantigen fitness modeling integrating clonal genealogy, epitope homology, and T cell receptor affinity. To examine in vivo T cell-neoantigen reactivity, we used functional assays in a subset of very long-term PDAC survivors (n=7, median OS 10.5 years).