| Autor: |
Thomas, Stacy K., Wattenberg, Max M., Choi-Bose, Shaanti, Uhlik, Mark, Harrison, Ben, Coho, Heather, Cassella, Christopher R., Stone, Meredith L., Patel, Dhruv, Markowitz, Kelly, Delman, Devora, Chisamore, Michael, Drees, Jeremy, Bose, Nandita, Beatty, Gregory L. |
| Předmět: |
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| Zdroj: |
Nature Communications; 10/10/2023, Vol. 14 Issue 1, p1-17, 17p |
| Abstrakt: |
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. The liver is the most common site of metastasis for pancreatic ductal adenocarcinoma (PDAC). Here, the authors demonstrate that β-glucan, a microbial component associated with trained immunity, activates liver-resident macrophages (Kupffer cells) and prevents PDAC metastasis to the liver [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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