Multidimensional Immunophenotyping of Intraductal Papillary Mucinous Neoplasms Reveals Novel T Cell and Macrophage Signature.

Conference Paper

BACKGROUND: 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 associated with dysplastic 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 11 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 (56%). Spatial profiling found that the T-cell infiltrate was significantly higher in regions of LGD compared with HGD (62% vs. 50%, p = 0.038). Macrophages were the only other immune cell type with > 10% abundance, yet conversely, were generally more abundant in regions of HGD compared to LGD (19% vs. 11%, p = 0.058). Correspondingly, immune cells within regions of HGD demonstrated transcriptional upregulation of genes associated with macrophage activity including secretion (CXCL1) and phagocytosis (C1QA, C1S, C4B). CONCLUSIONS: IPMN immune infiltrate is primarily composed of T cells and macrophages. Regions of HGD appear to be relatively deplete of T cells and show a trend toward macrophage enrichment compared with regions of LGD.

Full Text

Duke Authors

Cited Authors

  • Eckhoff, AM; Fletcher, AA; Landa, K; Iyer, M; Nussbaum, DP; Shi, C; Nair, SK; Allen, PJ

Published Date

  • November 2022

Published In

Volume / Issue

  • 29 / 12

Start / End Page

  • 7781 - 7788

PubMed ID

  • 35831529

Electronic International Standard Serial Number (EISSN)

  • 1534-4681

Digital Object Identifier (DOI)

  • 10.1245/s10434-022-12157-0

Conference Location

  • United States