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bioRxiv · 10.64898/2026.09.02.748262

Tumour rewires host tryptophan metabolism to promote organism-wide immune suppression

Garcia-Lopez, L.·Saez-Carrion, E.·Uribe, M. L.·Gomez-Escolar, C.·Ballesta-Illan, E.·Tennessen, J.·Dominguez, M.
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Abstract

How tumour genotype reshapes systemic metabolism to drive immune tolerance and tumour progression remains unclear. Here, we show that Pten-deficient Drosophila tumours reprogram host tryptophan metabolism, triggering systemic and local changes in immune and stromal compartments to foster tolerance. Tumour-derived nitric oxide activates the kynurenine pathway in liver-like tissue, selectively increasing the 3-hydroxykynurenine (3-HK) branch. Host 3-HK promotes tumour progression and suppresses immune function via aryl hydrocarbon receptor (AhR) signalling. These results identify the kynurenine pathway as a central tumour-host nexus and reveal how tumour genotype creates immune vulnerabilities.

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Garcia-Lopez, L., Saez-Carrion, E., Uribe, M. L., Gomez-Escolar, C., Ballesta-Illan, E., Tennessen, J., Dominguez, M.. 2026-09-03. Tumour rewires host tryptophan metabolism to promote organism-wide immune suppression. https://doi.org/10.64898/2026.09.02.748262

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