Expression profiling macrophage subsets [P1301]

Experiments expression profile several FACS-sorted pancreas tumor-associated macrophages. 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 originate during embryonic development and expand through in situ proliferation during tumor progression. While monocyte-derived TAMs play more potent roles in antigen presentation, embryonically derived TAMs exhibit a pro-fibrotic transcriptional profile, indicative of their role in producing and remodeling extracellular matrix molecules. Collectively, these findings uncover the heterogeneity of TAM origin and functions, and could provide therapeutic insight for PDAC treatment. Macrophages were either sorted from the normal pancreas or PDAC tissues of wild-type, or KPC or FLT3-CRE/LSL-YFP mice.