2021
DOI: 10.7150/thno.60679
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Abstract: Tryptophan (Trp)-catabolic enzymes (TCEs) produce metabolites that activate the aryl hydrocarbon receptor (AHR) and promote tumor progression and immunosuppression in glioblastoma. As therapies targeting TCEs or AHR become available, a better understanding of Trp metabolism is required. Methods: The combination of LC-MS/MS with chemical isobaric labeling enabled the simultaneous quantitative comparison of Trp and its amino group-bearing metabolites in multiple samples. We applied this m… Show more

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Cited by 19 publications
(9 citation statements)
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“…Higher AHR activity levels in patient tissues studied were associated with poorer patient survival. Interestingly, expression of these genes was found to be downregulated in GBM patient serum compared to controls (43).…”
Section: Tryptophan Metabolismmentioning
confidence: 96%
See 1 more Smart Citation
“…Higher AHR activity levels in patient tissues studied were associated with poorer patient survival. Interestingly, expression of these genes was found to be downregulated in GBM patient serum compared to controls (43).…”
Section: Tryptophan Metabolismmentioning
confidence: 96%
“…Taken together, Tryptophan degradation via IDO, resulting in kynurenine expression and AHR activation, has been shown to induce myeloid-and T cell-mediated immunosuppression (41)(42)(43). Additionally, low levels of Trp in GBM patient serum may be a contributing factor for the low efficacy of checkpoint inhibitor immunotherapies seen in GBM patients, given the evidence presented in a previous mouse study on the effects of generalized Trp metabolite dysregulation (41,43). These are promising takeaways that will increase our understanding of why checkpoint inhibitor immunotherapies are not effective for GBM patients and what we may do to increase efficacy (44).…”
Section: Tryptophan Metabolismmentioning
confidence: 99%
“…Alternatively, tryptophan can be metabolized by the kynurenine pathway to kynurenine and then quinolinic acid which can be converted to NAD+. The kynurenine pathway is hyperactive in glioblastoma [72,73] and it supports tumor development and progression [74,75], although perhaps not by engaging the aryl hydrocarbon receptor, AHR [76].…”
Section: Methionine Sam Transmethylation and Nad+mentioning
confidence: 99%
“…for key tumor metabolites 14 . In such scenarios, intensity weights in the CSR model are sampled from the intensities of the corresponding reference tissue, thus enabling probabilistic crosstissue comparisons.…”
Section: Fig 1b)mentioning
confidence: 99%