Abstract A25: Using biomaterial scaffolds to study the genesis of the immunosuppressive premetastatic niche in pancreatic cancer

CANCER RESEARCH(2019)

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摘要
Pancreatic cancer is a lethal malignancy with a 5-year survival rate of less than 10%. This poor prognosis is, in part, due to patients most often presenting with already metastatic disease. Pancreatic cancer is characterized by an abundant, reactive fibroinflammatory stroma, consisting of cancer-associated fibroblasts (CAFs) and infiltrating immune cells that send and receive signals to and from other nearby cells, including the tumor cells. The crosstalk between tumor cells and elements of the stroma results in an immunosuppressive tumor microenvironment both at the primary tumor and the sites of metastases. A key limitation in studying metastatic disease in mouse models is the inability to predict when the cancer cells will ultimately metastasize. In this study biomaterial scaffolds that mimic the premetastatic niche in vivo, by attracting immune cells followed by tumor cells, were used to longitudinally follow the metastasis process in individual animals. Biomaterial scaffolds were implanted subcutaneously to mimic the premetastatic niche in both syngeneic and spontaneous mouse (iKras* p53*) models of pancreatic cancer. Scaffolds were harvested 21 days post implantation and taken for histologic analysis to characterize the cellular infiltrate in response to the primary tumor. Histologic analysis (HE 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A25.
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