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Published on: December 7, 2019
Bacteria-derived 3-hydroxydodecanoic acid induces a potent anti-tumor immune response via the GPR84 receptor
Egle Katkeviciute1, Anna Bircher2, Rocio Sanchez2
1Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; Recolony AG, 8092 Zurich, Switzerland.
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.
Insights
Bacteria-derived 3-hydroxydodecanoic acid shows potent anti-tumor effects by activating GPR84 receptor signaling. This metabolite enhances CD8+ T cell activity, offering a promising new avenue for cancer therapy and targeting GPR84.
Area of Science:
- Microbiology
- Immunology
- Metabolomics
Background:
- Cancer treatment requires novel therapeutic strategies.
- Bacteria-derived metabolites are emerging as potential anti-cancer agents.
Purpose of the Study:
- To investigate bacteria-derived metabolites for cancer therapy.
- To explore the anti-tumor potential of 3-hydroxydodecanoic acid and its mechanism via GPR84 signaling.
Main Methods:
- Detection of 3-hydroxydodecanedioic acid in tumor-bearing mice serum.
- Evaluation of 3-hydroxydodecanoic acid's anti-tumor effects in cancer models.
- Analysis of GPR84 receptor signaling and CD8+ T cell infiltration.
- Metabolomics analysis of colorectal cancer patient serum.
Main Results:
- 3-hydroxydodecanoic acid demonstrates significant anti-tumor activity.
- The anti-tumor effect is mediated through GPR84 receptor signaling.
- Enhanced CD8+ T cell infiltration and cytotoxicity were observed in tumors.
- Lower levels of these metabolites correlate with advanced colorectal cancer stages.
Conclusions:
- 3-hydroxydodecanoic acid is a promising bacteria-derived metabolite for cancer treatment.
- The GPR84 receptor is a potential therapeutic target for enhancing anti-tumor immunity.
- These findings support the development of metabolite-based cancer therapies.
