@article{d5c53f929a364d01aa57cf4979322143,
title = "Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression",
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",
author = "Yu Zhu and Herndon, {John M.} and Sojka, {Dorothy K.} and Kim, {Ki Wook} and Knolhoff, {Brett L.} and Chong Zuo and Cullinan, {Darren R.} and Jingqin Luo and Bearden, {Audrey R.} and Lavine, {Kory J.} and Yokoyama, {Wayne M.} and Hawkins, {William G.} and Fields, {Ryan C.} and Randolph, {Gwendalyn J.} and DeNardo, {David G.}",
note = "Funding Information: The authors acknowledge support from an award from the American Association for Cancer Research and Pancreatic Cancer Action Network, National Cancer Institute (NCI) awards R01-CA177670, R01-CA203890, P50-CA196510, T32CA009621, UL1TR000448, and P30-CA91842, and the BJC Institute of Health and Siteman Cancer Center Cancer Frontier Fund. Microarray analyses were performed by the Genome Technology Access Center at Washington University and were partially funded by NCI award P30-CA91842 NCRR UL1RR024992. The authors also acknowledge Grant Gould and Hans Challen for help on irradiation experiments, Liping Yang for help on parabiosis, and Daniel C. Link, Jason C. Mills, Boris Calderon, and Jesse W. Williams for advice. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = aug,
day = "15",
doi = "10.1016/j.immuni.2017.07.014",
language = "English",
volume = "47",
pages = "323--338.e6",
journal = "Immunity",
issn = "1074-7613",
number = "2",
}