Abstract 3951: Spatial mapping of B7-H3 mediated cellular plasticity in treatment naive pancreatic cancer

作者：Assya Legrini, Tengyu Zhang, Mari-Claire McGuigan, Colin Wood, Luke McNickle, Claire Kennedy-Dietrich, Ghazal Latifi, Yoana Doncheva, Josefina Vasquez, Hannah Morgan, Pamela McCall, Michail Doukas, J. Edwards, Nigel B. Jamieson · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.am2026-3951 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Pancreatic and Hepatic Oncology Research

Abstract Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most lethal cancers, with only 20% of patients surviving 5 years post pancreatectomy. Despite rationale for targeting immune pathways, existing immunotherapies have provided minimal benefit to date. The immune checkpoint molecule, B7-H3, has emerged as a promising therapeutic target across solid tumours. However, its cellular origins, spatial context and clinical relevance in PDAC is poorly defined. This study aims to address this unmet need. An integrated spatial multi-omics strategy was applied across two treatment naïve PDAC cohorts. These FFPE tissue microarrays were divided into a test cohort (n=27), and a validation cohort (n=74). GeoMx regional proteomics (Bruker) was applied on section of the test cohort, while GeoMx regional whole transcriptome (Bruker), CosMx single cell 64-plex protein (Bruker) and CosMx 6K RNA (Bruker) assays were applied to serial sections of the validation cohort. Additional CosMx single cell whole transcriptome (WTx) data was generated from an Intraductal Papillary Mucinous Neoplasm (IPMN) whole section cohort (n=6). GeoMx samples were fluorescently stained with Syto13, PanCk, CD45 and αSMA, and masks were selected for PanCk+ve epithelium and tumour microenvironment (TME). CosMx samples were fluorescently stained for DAPI, PanCk, CD298/B2M, CD45 and CD68. Extensive clinicopathological data was available for all samples. Across regional protein and transcriptome profiling, B7-H3...