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:
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:
URI: https://repository.cshl.edu/id/eprint/38181

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