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Articles

A stromal PAI1-tPA axis orchestrates immunosuppression in pancreatic cancer

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By Kantaro Murayama, Guanglin He, Nooshin Zandi, Tenzin Ngodup, Ashley Mello, Miranda Liu, Yaqing Zhang, Jiaqi Shi, Yatrik M Shah, Daniel Lawrence, Kyoung Eun Lee, Brynn Elson, Sean Hannifin
| Science Magazine Verified
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a dense desmoplastic stroma and an immunosuppressive tumor microenvironment that contribute to therapeutic resistance. Here, we identify plasminogen activator inhibitor 1 (PAI1) as a stroma-derived mediator of immune evasion and tumor progression in PDAC. PAI1 is predominantly produced and secreted by cancer-associated fibroblasts, and its genetic ablation in the stromal compartment impairs tumor growth.
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