biostudies-literatureGuinn SJane and Aatos Erkko FoundationRelander FoundationInstrumentariumin TiedesäätiöiCAN precision medicine of the Finnish academyStand Up to Cancer-LustgartenNIH/NCISigrid Juséliuksen SäätiöEmil Aaltosen SäätiöLustgarten FoundationNCI NIH HHSHopper-Belmont FoundationStand Up To Cancer - Lustgarten1517-1533https://www.ebi.ac.uk/biostudies/studies/S-EPMC11065624biostudies-literatureUnknown84(9)Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in Cancer researchTransfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.PMC11065624P01 CA247886P30 CA006973P30CA006973K08 CA248710P01CA2478862015-002SU2C-AACR-DT26-17R50 CA243627F31 CA284525U01CA253403U01 CA253403Elisseeff JHMitchell JTSidiropoulos DNLoth MStein-O'Brien GYu JDanilova LSeppala TTCherry CJaffee EMGupta AKartalia EZlomke HTandurella JAZheng LTing DTWood LDRyan DPFertig EJPatel JKagohara LTZabransky DJSuri RHe JKimmelman AWolfgang CLKinny-Koster BLyman MRRamani MLee JWBurkhart RAGuinn SPucsek ABZimmerman JWfalseTransfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in 2024-01-01T00:00:00Z2024 May2026-06-02T06:20:37.979Z2025-04-04T09:58:35.352ZS-EPMC110656243858755210.1158/0008-5472.can-23-166010.1158/0008-5472.CAN-23-1660