Through single-cell RNA sequencing of pancreatic ductal adenocarcinoma (PDAC), Elyada et al. confirmed the two known cancer-associated fibroblast (CAF) subsets: ɑSMA+ myofibroblastic mCAFs and cytokine and chemokine-expressing inflammatory iCAFs. Both mouse and human PDAC contained a third, novel subset named antigen-presenting CAFs (apCAFs) enriched in MHC II-related genes and antigen processing and presentation pathways, which were capable of activating CD4+ T cells ex vivo. Suppressive cell types dominated the immune portion of human and mouse PDAC, with reduced TILs in mice.
Contributed by Alex Najibi
Cancer-associated fibroblasts (CAFs) 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 employ 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 (myCAFs) and inflammatory CAFs (iCAFs) 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 classical co-stimulatory molecules. We term this cell population "antigen-presenting CAFs" (apCAFs), and find that they activate CD4+ T cells in an antigen-specific fashion in a model system, confirming their putative immune-modulatory capacity. Our cross-species analysis paves the way for investigating distinct functions of CAF subtypes in PDAC immunity and progression.
Author Info: (1) Cancer Center, Cold Spring Harbor Laboratory. (2) Jackson Laboratory. (3) Department of Systems Biology, Columbia University. (4) Computational Sciences, Jackson Laboratory. (5
Author Info: (1) Cancer Center, Cold Spring Harbor Laboratory. (2) Jackson Laboratory. (3) Department of Systems Biology, Columbia University. (4) Computational Sciences, Jackson Laboratory. (5) Single Cell Biology, Jackson Laboratory. (6) Hepatobiliary and Pancreatic Surgery, Johns Hopkins University. (7) Department of Surgery, The Johns Hopkins Medical Institutions. (8) Cold Spring Harbor Laboratory. (9) Cancer Center, Cold Spring Harbor Laboratory. (10) Cancer Biology, Cold Spring Harbor Laboratory. (11) The Jackson Laboratory for Genomic Medicine. (12) Department of Oncology, Division of Gastrointestinal Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University. (13) Regulatory Biology Laboratory, Salk Institute for Biological Studies. (14) Medicine, Memorial Sloan Kettering Cancer Center. (15) BSR, Cold Spring Harbor Laboratory. (16) Department of Surgery, Johns Hopkins Medical Institutions. (17) Cold Spring Harbor Laboratory. (18) Cancer Center, Cold Spring Harbor Laboratory. (19) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University. (20) Department of Systems Biology, Columbia University. (21) Single Cell Biology Laboratory, The Jackson Laboratory for Genomic Medicine. (22) Cold Spring Harbor Laboratory dtuveson@cshl.edu.
