Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies
Jaewon J. Lee, Vincent Bernard, Alexander Semaan, Maria E. Monberg, Jonathan Huang, Bret M. Stephens, Daniel Lin, Kimal Rajapakshe, Brian Weston, Manoop S. Bhutani, Cara Haymaker, Chantale Bernatchez, Cullen M. Taniguchi, Anirban Maitra, Paola A. Guerrero
Abstract
PURPOSE: Precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC) are imperative for improving disease outcomes. With molecular subtypes of PDAC gaining relevance in the context of therapeutic stratification, the ability to characterize heterogeneity of cancer-specific gene expression patterns is of great interest. In addition, understanding patterns of immune evasion within PDAC is of importance as novel immunotherapeutic strategies are developed. EXPERIMENTAL DESIGN: Single-cell RNA sequencing (scRNA-seq) is readily applicable to limited biopsies from human primary and metastatic PDAC and identifies most cancers as being an admixture of previously described epithelial transcriptomic subtypes. RESULTS: Integrative analyses of our data provide an in-depth characterization of the heterogeneity within the tumor microenvironment, including cancer-associated fibroblast subclasses, and predicts for a multitude of ligand-receptor interactions, revealing potential targets for immunotherapy approaches. CONCLUSIONS: biopsies from patients with PDAC paired with scRNA-seq may facilitate therapeutic prediction from limited biopsy samples.