Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts

Elyada, E., Bolisetty, M., Laise, P., Flynn, W. F., Courtois, E. T., Burkhart, R. A., Teinor, J. A., Belleau, P., Biffi, G., Lucito, M. S., Sivajothi, S., Armstrong, T. D., Engle, D. D., Yu, K. H., Hao, Y., Wolfgang, C. L., Park, Y., Preall, J., Jaffee, E. M., Califano, A., Robson, P., Tuveson, D. A. (June 2019) Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov, 9 (8). pp. 1102-1123. ISSN 2159-8274

Abstract

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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders Investigative techniques and equipment diseases & disorders > neoplasms organism description > animal Investigative techniques and equipment > assays organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent Investigative techniques and equipment > assays > Single cell sequencing
CSHL Authors:	Elyada, Ela Belleau, Pascal Biffi, Giulia Lucito, Matthew S Engle, Dannielle Hao, Yuan Park, Youngkyu Preall, Jonathan Tuveson, David A.
Communities:	CSHL Cancer Center Program > Cellular Communication in Cancer Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL labs > Preall lab CSHL labs > Tuveson lab CSHL Cancer Center Shared Resources > Animal Shared Resource
Depositing User:	Matthew Dunn
Date:	13 June 2019
Date Deposited:	19 Jul 2019 19:24
Last Modified:	02 Feb 2024 14:55
PMCID:	PMC6727976
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/38181

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