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Immunity. 2017 Aug 15;47(2):323-338.e6. doi: 10.1016/j.immuni.2017.07.014.

Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression.

Author information

1
Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
2
Department of Rheumatology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
3
Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
4
Department of Surgery, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
5
Division of Biostatistics, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
6
Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
7
Department of Rheumatology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Howard Hughes Medical Institute, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
8
Siteman Cancer Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Surgery, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
9
Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
10
Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA. Electronic address: ddenardo@wustl.edu.

Abstract

Tumor-associated macrophages (TAMs) are essential components of the cancer microenvironment and play critical roles in the regulation of tumor progression. Optimal therapeutic intervention requires in-depth understanding of the sources that sustain macrophages in malignant tissues. In this study, we investigated the ontogeny of TAMs in murine pancreatic ductal adenocarcinoma (PDAC) models. We identified both inflammatory monocytes and tissue-resident macrophages as sources of TAMs. Unexpectedly, significant portions of pancreas-resident macrophages originated from embryonic development and expanded through in situ proliferation during tumor progression. Whereas monocyte-derived TAMs played more potent roles in antigen presentation, embryonically derived TAMs exhibited a pro-fibrotic transcriptional profile, indicative of their role in producing and remodeling molecules in the extracellular matrix. Collectively, these findings uncover the heterogeneity of TAM origin and functions and could provide therapeutic insight for PDAC treatment.

KEYWORDS:

fibrosis; macrophage ontogeny; pancreas; pancreatic cancer; tissue-resident macrophage; tumor immunity

Comment in

PMID:
28813661
PMCID:
PMC5578409
DOI:
10.1016/j.immuni.2017.07.014
[Indexed for MEDLINE]
Free PMC Article

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