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

Cancer discovery, 2019-08, Vol.9 (8), p.1102-1123

2019 American Association for Cancer Research. ;ISSN: 2159-8274 ;EISSN: 2159-8290 ;DOI: 10.1158/2159-8290.cd-19-0094 ;PMID: 31197017

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Title:
Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts
Author: Elyada, Ela ; Bolisetty, Mohan ; Laise, Pasquale ; Flynn, William F ; Courtois, Elise T ; Burkhart, Richard A ; Teinor, Jonathan A ; Belleau, Pascal ; Biffi, Giulia ; Lucito, Matthew S ; Sivajothi, Santhosh ; Armstrong, Todd D ; Engle, Dannielle D ; Yu, Kenneth H ; Hao, Yuan ; Wolfgang, Christopher L ; Park, Youngkyu ; Preall, Jonathan ; Jaffee, Elizabeth M ; Califano, Andrea ; Robson, Paul ; Tuveson, David A
Subjects: Animals ; Antigen Presentation - immunology ; Cancer-Associated Fibroblasts - immunology ; Cancer-Associated Fibroblasts - metabolism ; Cancer-Associated Fibroblasts - pathology ; Carcinoma, Pancreatic Ductal - etiology ; Carcinoma, Pancreatic Ductal - metabolism ; Carcinoma, Pancreatic Ductal - pathology ; Fluorescent Antibody Technique ; Histocompatibility Antigens Class II - genetics ; Histocompatibility Antigens Class II - immunology ; Humans ; Mice ; Models, Biological ; Pancreatic Neoplasms - etiology ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Single-Cell Analysis ; Tumor Microenvironment - immunology
Is Part Of: Cancer discovery, 2019-08, Vol.9 (8), p.1102-1123
Description: 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 . Moreover, we describe a new population of CAFs that express MHC class II and CD74, but do not express classic costimulatory molecules. We term this cell population "antigen-presenting CAFs" 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. SIGNIFICANCE: Appreciating the full spectrum of fibroblast heterogeneity in pancreatic ductal adenocarcinoma is crucial to developing therapies that specifically target tumor-promoting CAFs. This work identifies MHC class II-expressing CAFs with a capacity to present antigens to CD4 T cells, and potentially to modulate the immune response in pancreatic tumors. . .
Publisher: United States
Language: English
Identifier: ISSN: 2159-8274
EISSN: 2159-8290
DOI: 10.1158/2159-8290.cd-19-0094
PMID: 31197017
Source: MEDLINE
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Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts

2019 American Association for Cancer Research. ;ISSN: 2159-8274 ;EISSN: 2159-8290 ;DOI: 10.1158/2159-8290.cd-19-0094 ;PMID: 31197017

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