Programmable immunoprobiotics orchestrate antitumor immune response with Pin1 inhibition for pancreatic cancer treatment

• 成果类型: Article
• 署名作者: Yuan, Sichen; Yang, Xicheng; Bremmer, Alexa M.; Wang, Yixin; Li, Sherry; Chen, Yu; You, Yawen; Hu, Quanyin
• 署名单位: University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15229
• DOI: 10.1073/pnas.2507711122
• 发表日期: 2025-08-26
• 关键词: prolyl isomerase pin1; salmonella-typhimurium; bacteria; induction; depletion; therapy; dextran

摘要

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options due to its desmoplastic and immunosuppressive tumor microenvironpoint blockade (ICB) has shown poor efficacy in PDAC, partly due to the desmoplastic stroma and low immunogenicity. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) promotes both fibrosis and immune evasion, making it a compelling target PD-L1 blockade to enhance immunotherapy. This system uses Escherichia coli Nissle to PDAC, enabling sustained release to degrade the fibrotic stroma and upregulate enhances immune cell infiltration, and improves antitumor response while minimizpromising platform to overcome immunotherapy resistance in solid tumors.