Abstract A127: Role of Macrophage Subsets in Liver Metastasis

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal disease and frequently metastasize to the liver. The presence of macrophages (F4/80+ cells or CD68+ cells) is reported to correlate with tumor progression and metastasis in pancreatic cancer. Emerging evidence has revised the traditional concept of macrophage ontogeny and made it increasingly apparent that there exists functional diversity between resident macrophages originating from yolk sac erythro-myeloid progenitors (EMPs) and hematopoietic stem cells (HSCs)-derived macrophages. Sophisticated therapeutic intervention requires in-depth understanding of these macrophage subsets in the metastasis microenvironment. However, the role and heterogeneity of macrophages in tumor development, in particular in PDAC liver metastasis, remains poorly understood. Here, we utilized murine PDAC model to inidcate that Kupffer cells and tumor associated macrophages (TAMs) are two developmentally and functionally distinct subsets of macrophages. Removal of Kupffer cells by depletion of Id3 in macrophage progenitors or CSF1R blockade increases tumor burden. These findings reveal that Kupffer cells play a key role in restraining PDAC liver metastasis and show the necessity to understand macrophage origin when developing therapeutics for cancer treatment. Citation Format: Zihou Deng, Frederic Geissmann. Role of macrophage subsets in liver metastasis [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A127.