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

Highlights

• Serum transfer from CC4-treated mice reduces tumors and enhances CD8+ T cell activity

• 3OH Dodeca’s anti-tumor effect requires GPR84 activation and IL-12 production

• The therapeutic potential of 3OH Dodeca extends to diverse solid tumors

• Human CRC tumors exhibit reduced levels of Dodeca and 3OH Diacid in advanced stages

Summary

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.

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