2. Academic Validation
  3. Bacteria-derived 3-hydroxydodecanoic acid induces a potent anti-tumor immune response via the GPR84 receptor

Bacteria-derived 3-hydroxydodecanoic acid induces a potent anti-tumor immune response via the GPR84 receptor

  • Cell Rep. 2025 Feb 26;44(3):115357. doi: 10.1016/j.celrep.2025.115357.
Egle Katkeviciute 1,  Anna Bircher 2,  Rocio Sanchez 2,  Martin Schwill 3,  Andrea Dorst 4,  Yasser Morsy 2,  Javier Conde 5,  Nicola Zamboni 6,  Karl Gademann 4,  Michael Scharl 7,  Ana Montalban-Arques 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; Recolony AG, 8092 Zurich, Switzerland.
  • 2 Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • 3 Recolony AG, 8092 Zurich, Switzerland.
  • 4 Department of Chemistry, University of Zurich, 8057 Zurich, Switzerland.
  • 5 Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; Department of Molecular and Cellular Gastroenterology, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
  • 6 Institute of Molecular Systems Biology, Federal Institute of Technology Zurich, 8093 Zurich, Switzerland.
  • 7 Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland. Electronic address: michael.scharl@usz.ch.
PMID: 40014452 DOI: 10.1016/j.celrep.2025.115357
Abstract

Despite advances in Cancer treatment, the development of effective therapies remains an urgent unmet need. Here, we investigate the potential of bacteria-derived metabolites as a therapeutic alternative for the treatment of Cancer. We detect 3-hydroxydodecanedioic acid in the serum of tumor-bearing mice treated with serum from mice previously supplemented with a mix of Clostridiales bacteria. Further, 3-hydroxydodecanoic acid, an intermediate derivative between dodecanoic and 3-hydroxydodecanedioic acids, exhibits a strong anti-tumor response via GPR84 receptor signaling and enhances CD8+ T cell infiltration and cytotoxicity within tumor tissue in multiple Cancer models. Metabolomics analysis of colorectal Cancer patient serum reveals an inverse correlation between the abundance of these metabolites and advanced disease stages. Our findings provide a strong rationale for 3-hydroxydodecanoic acid and the GPR84 receptor to be considered as promising therapeutic targets for Cancer treatment.

Keywords

3-hydroxydodecanoic acid; 3-hydroxylauric acid; CP: Cancer; CP: Microbiology; GPR84 receptor; MCFA; T cells; bacteria-derived metabolites; cancer; immunotherapy; macrophages.

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