General Surgery Resident Duke University Durham, North Carolina, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Participants should be aware of the following financial/non-financial relationships:
Austin M. Eckhoff, MD: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Introduction: Intraductal papillary mucinous neoplasms (IPMN) are the only radiographically identifiable precursor to pancreatic adenocarcinoma, yet little is known about how these lesions progress to cancer. Inflammation has been found to be associated with progression, however the cause and composition of this inflammation remains poorly characterized. We sought to comprehensively profile immune cell infiltration using parallel spatial transcriptomic and flow cytometric techniques.
Methods: Twelve patients with resected IPMN exhibiting both high-grade dysplasia (HGD) and low-grade dysplasia (LGD) were selected for spatial transcriptomics (NanoString GeoMx). Immune (CD45+), epithelial (PanCK+), and stromal (SMA+) compartments were analyzed separately using the GeoMx NGS Pipeline. An additional 14 patients resected for IPMN of varying degrees of dysplasia underwent immunophenotyping using flow cytometry (DURAClone IM).
Results: Spatial transcriptomics revealed that T cells represent the dominant immune cell within IPMN stroma which was confirmed by flow cytometry (53.8%, IQR 43.3-68.3%).Spatial profiling found that the T cell infiltrate was significantly higher in regions of LGD compared to HGD (61.6% vs 49.7%, p = 0.048). Macrophages were the only other immune cell type with >10% abundance, yet conversely, were generally more abundant in regions of HGD compared to LGD (18.5% vs. 11.3%, p = 0.068). Correspondingly, immune cells within regions of HGD demonstrated transcriptional upregulation of genes associated with macrophage activity, including differentiation (MCLi), secretion (CXCL1), and phagocytosis (C3, C4B, FGCR2A/B). All other immune cell types were infrequently seen and were not differentially abundant between HGD versus LGD stroma.
Conclusions: IPMN immune infiltrate is primarily composed of T cells and macrophages. Regions of HGD appear to be enriched for macrophages and relatively deplete of T cells compared to regions of LGD. This is supported by a transcriptional signature of pro-inflammatory macrophage activity in the regions of HGD.Further studies are needed to understand the interplay between T cells and macrophages and how this drives malignant progression.
Learning Objectives:
To describe the immune infiltrates present within IPMN stroma and how the immune infiltrate differs in high-grade dysplasia and low-grade dysplasia.
To explain transcriptional gene and pathway upregulation present in high-grade dysplasia in IPMN stroma.
To understand new techniques in profiling the tumor microenvironment and transcriptional gene upregulation.
