Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts

Abstract Cancer-associated fibroblasts (CAF) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although the extent of CAF heterogeneity has remained undefined. Here we use single-cell RNA sequencing to thoroughly characterize the neoplastic and tumor microenvironment content of human and mouse PDAC tumors. We corroborate the presence of myofibroblastic CAFs and inflammatory CAFs and define their unique gene signatures in vivo. Moreover, we describe a new population of CAFs that express MHC class II and CD74, but do not express classic costimulatory molecules. We term…

• SF
  Simons Foundation

  Award: 552716
• LF
  Lustgarten Foundation
• NI
  National Institutes of Health

  Awards: R01CA188134, U01CA224013, R33CA206949, P50CA101955, U10CA180944, S10 OD012351, U01CA210240, P20CA192996, R50 CA211506-02, U01CA168409, R01CA190092, P30CA045508, S10 OD0217640
• NC
  National Cancer Institute

  Awards: R01 CA18492-04, R01 CA19729603, R35 CA197745