Abstract A91: T-cell regulation in pancreatic ductal adenocarcinoma

Abstract

Background: Pancreatic cancer has the worst prognosis of any human malignancy. We have shown using transcriptomics and histopathology that immune infiltrate in resection samples from a Whipple’s operation is predictive of prognosis. In particular, lymphocytes appear to be a major prognostic marker. With promising immunotherapies being proposed for other cancers, there is a need for a deeper understanding of the immune landscape of pancreatic cancer to identify points of intervention. Methods: We have developed a 37-marker mass cytometry staining panel to characterize the dominant immune populations within primary pancreatic cancer. Our panel further analyzes T-cell subpopulations and their functional status, including a host of clinically relevant checkpoint markers and immunosuppressive signatures. Results: The degree of immune infiltration we observe is highly variable between patients, but all patients equivocally show a complex immune microenvironment consistent of macrophages, neutrophils, and different lymphocytes. The T cells infiltrating the tumor, both CD4 and CD8 T cells, appear to be dysfunctional with hardly any activation signature. A highly suppressive phenotype also characterizes the regulatory T-cell population. Our data suggest that the microenvironment of pancreatic cancer is extremely suppressive and could be a major driver of poor prognosis. Yet, this work identifies potential therapeutic targets and avenues that should be further investigated and may inspire future clinical trials. Future Work: We are planning to investigate the behavior of T-regs from PDAC using in vitro assays. To that end, we will use a recently developed advanced 3D culture system to visualize their interactions with CD8s and the functional consequences of those interactions on CD8-mediated killing. Citation Format: Shivan Sivakumar, Enas Abu-Shah, David Ahern, Nagina Mangal, Srikanth Reddy, Aniko Rendek, Zahir Soonawalla, Michael Silva, Mark Middleton, Michael L. Dustin. T-cell regulation in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A91.