转移
库普弗电池
免疫系统
胰腺癌
巨噬细胞极化
癌症研究
巨噬细胞
医学
癌细胞
病理
癌症
免疫学
生物
内科学
体外
生物化学
作者
Stacy K. Thomas,Max M. Wattenberg,Shaanti Choi-Bose,Mark Uhlik,Ben Harrison,Heather Coho,Christopher R. Cassella,Maureen Stone,Dhruv Patel,Kelly Markowitz,Devora Delman,Michael Chisamore,Jeremy Drees,Nandita Bose,Gregory L. Beatty
标识
DOI:10.1038/s41467-023-41771-z
摘要
Abstract Although macrophages contribute to cancer cell dissemination, immune evasion, and metastatic outgrowth, they have also been reported to coordinate tumor-specific immune responses. We therefore hypothesized that macrophage polarization could be modulated therapeutically to prevent metastasis. Here, we show that macrophages respond to β-glucan (odetiglucan) treatment by inhibiting liver metastasis. β-glucan activated liver-resident macrophages (Kupffer cells), suppressed cancer cell proliferation, and invoked productive T cell-mediated responses against liver metastasis in pancreatic cancer mouse models. Although excluded from metastatic lesions, Kupffer cells were critical for the anti-metastatic activity of β-glucan, which also required T cells. Furthermore, β-glucan drove T cell activation and macrophage re-polarization in liver metastases in mice and humans and sensitized metastatic lesions to anti-PD1 therapy. These findings demonstrate the significance of macrophage function in metastasis and identify Kupffer cells as a potential therapeutic target against pancreatic cancer metastasis to the liver.
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