2. Academic Validation
  3. Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice

Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice

  • Nat Commun. 2023 Oct 10;14(1):6330. doi: 10.1038/s41467-023-41771-z.
Stacy K Thomas 1 2,  Max M Wattenberg 1 2,  Shaanti Choi-Bose 1 2,  Mark Uhlik 3 4,  Ben Harrison 3,  Heather Coho 1 2,  Christopher R Cassella 1 2,  Meredith L Stone 1 2,  Dhruv Patel 1 2,  Kelly Markowitz 1 2,  Devora Delman 1 2,  Michael Chisamore 5,  Jeremy Drees 3,  Nandita Bose 3,  Gregory L Beatty 6 7
Affiliations

Affiliations

  • 1 Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 2 Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 3 HiberCell Inc, Roseville, MN, USA.
  • 4 OncXerna, Waltham, MA, USA.
  • 5 Merck & Co., Inc., Kenilworth, NJ, USA.
  • 6 Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. gregory.beatty@pennmedicine.upenn.edu.
  • 7 Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. gregory.beatty@pennmedicine.upenn.edu.
PMID: 37816712 DOI: 10.1038/s41467-023-41771-z
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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