Editors' ChoiceGlioma

The Great Escape

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Science Translational Medicine  19 Oct 2011:
Vol. 3, Issue 105, pp. 105ec169
DOI: 10.1126/scitranslmed.3003304

There is a common belief, especially around the holidays, that the tryptophan in turkey makes you sleepy. However, actual scientific evidence doesn’t support this claim—droopy eyes after a big meal is more likely rooted in a full stomach and a desire to avoid washing dishes than in turkey consumption. Yet, tryptophan does have a suppressive function in your body—its degradation has been linked to cancer-associated immune escape. Now, Opitz et al. report that the tryptophan degradation product kynurenine binds the aryl hydrocarbon receptor (AHR), suppressing the antitumor immune response and enhancing tumor cell survival.

The AHR is best known to bind to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), an environmental toxin produced as a byproduct from industrial processes that suppresses the immune system and promotes tumorigenesis. Opitz et al. report that cells from glioma, a type of brain tumor, may up-regulate the liver enzyme tryptophan dioxygenase (TDO) and promote tryptophan consumption. They further report that the tryptophan catabolite kynurenine, a product of TDO, is the endogenous ligand that activates the AHR and that this activation of the AHR by kynurenine leads to immune suppression and increased tumor invasion. Indeed, this pathway is associated with poor prognosis in glioma patients and may extend to other cancers as well.

These new findings may explain one way that cancer cells win their tug of war with the immune system: Activation of AHR by kynurenine may simultaneously suppress immune function and promote tumorigenesis. By increasing their consumption of tryptophan, tumor cells are engineering their own great escape.

C. A. Opitz et al., An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 478, 197–203 (2011). [Abstract]

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