Abstract B37: The complex immune-microenvironment heterogeneity in pancreatic cancer

Abstract

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy, resulting in more than 3,000 deaths per year in The Netherlands. The tumor microenvironment (TME) contributes largely to the treatment failure of the disease. TME consists of the stromal compartment, extracellular matrix, and tumor-infiltrative lymphocytes (TILs). Types and numbers of TILs are associated with clinical outcome, i.e., highCD8+: FOXP3 ratio is linked to a favorable prognosis. However, the intratumor immune variation in pancreatic cancer has not been studied so far. This study aims at investigating the differences of the immune infiltration within various areas of the same pancreatic cancer samples (intratumor variation) and comparing to healthy controls (extratumor variation). Such differences may be used for microenvironment remodeling, which may open new therapeutic approaches for PDAC patients. Materials and Methods: Formalin-fixed, paraffin-embedded (FFPE) samples of 26 PDAC patients and 8 healthy controls were selected. RNA was isolated separately from the tumor core and from the adjacent normal-like pancreatic tissue of the same sample. Immune profiling was carried out using the PanCancer Immune Profiling Panel of Nanostring technology. Subsequently, the gene expression data were analyzed using nSolver basic software and the advanced module. Results: The immune infiltration in the core of PDAC samples was different from that in the adjacent normal-like areas of the same patients. Tumor samples exhibited the lowest CD8+, Th1, neutrophil, and Natural Killer cell infiltration as compared to normal-like areas. In addition, the normal-like areas of PDAC samples showed a different immune profile as compared to the healthy controls. B lymphocytes were significantly higher in healthy controls compared to normal-like PDAC samples. Discussion and Conclusion: Our results present the variation in the immune microenvironment between the normal-like pancreatic tissue and the healthy pancreas, indicating that changes at the immune levels precede morphologic changes, tumorigenesis, and tumor cell infiltration. Additionally, specific changes in TILs occur in a gradient fashion from adjacent normal-like tissue to the tumor core. Understanding the differences of the immune microenvironment in the same tissue samples will enable developing an accurate microenvironment remodeling therapeutic approaches to treat PCDA patients. Citation Format: Frederieke Grevers, Diba Latifi, Willem de Koning, Casper H.J. van Eijck, Dana A. Mustafa. The complex immune-microenvironment heterogeneity in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B37.