Abstract C026: Single-cell multi-omics in pancreatic cancer reveals differential immune evasion mechanisms between prognostic groups

Abstract

Abstract Pancreatic cancer has the worst survival of any human cancer with a 5 year survival of less than 10% with minimal treatment options. We have previously made the observation that patients with a T cell infiltrate in their primary tumor have a better prognosis then those that do not. To understand the nature of the immune infiltrate, we have in 12 patients performed 10X sequencing on CD45 cells from the tumor as well as single cell TCR-seq, BCR-seq and cite-seq and have performed the same experiment on the matching PBMCs. We have generated a dataset of approximately 185000 cells with half coming from the tumor. This unravels a complex immune infiltrate with the predominant immune cell types consisting of T cells. Our data shows that within the tumor infiltrate, patients either have high or low myeloid infiltration. We see a highly active Treg population that has multiple checkpoints activated. Using TCR data, we saw the biggest clonal expansions in CD8 EM, CD8 senescent cells and Tregs. Circulating TIL CD4 T cells are dominated by activated Tregs, Tfh, and Th2 and circulating TIL CD8 T cells are dominated by CD8 EM T cells. Our work identifies multiple novel therapeutic targets that should form the basis for rational design of a new generation of clinical trials in pancreatic ductal adenocarcinoma. Citation Format: Shivan Sivakumar, Ashwin Jainarayanan, Edward Arbe-Barnes, Enas Abu-Shah, Rachael Bashford-Rogers. Single-cell multi-omics in pancreatic cancer reveals differential immune evasion mechanisms between prognostic groups [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C026.