| First Author | Thomas SK | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 6330 |
| PubMed ID | 37816712 | Mgi Jnum | J:342459 |
| Mgi Id | MGI:7540046 | Doi | 10.1038/s41467-023-41771-z |
| Citation | Thomas SK, et al. (2023) Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice. Nat Commun 14(1):6330 |
| abstractText | 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 beta-glucan (odetiglucan) treatment by inhibiting liver metastasis. beta-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 beta-glucan, which also required T cells. Furthermore, beta-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. |
