Tryptophan metabolism in brain tumors - IDO and beyond.
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ABSTRACT:
SUBMITTER: Platten M
PROVIDER: S-EPMC8373719 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
Tryptophan metabolism in brain tumors - IDO and beyond.
Platten Michael M Friedrich Mirco M Wainwright Derek A DA Panitz Verena V Opitz Christiane A CA
Current opinion in immunology 20210401
Metabolism of the essential amino acid tryptophan is a key metabolic pathway that restricts antitumor immunity and is a drug development target for cancer immunotherapy. Tryptophan metabolism is active in brain tumors including gliomas and promotes a malignant phenotype and contributes to the immunosuppressive tumor microenvironment. In recent years, improved understanding of the regulation and downstream function of tryptophan metabolism has been significantly expanded beyond the initial in vit ...[more]
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Project description:Patients with brain tumors have an increased risk for depression, whose underlying pathomechanism may involve dysregulated tryptophan/kynurenine metabolism. In this study, we analyzed the relation of depressive symptoms to clinical and tumor characteristics as well as cerebral and systemic tryptophan metabolism in patients with primary brain tumors. Sixty patients with newly-diagnosed or recurrent primary brain tumor underwent testing with the Beck Depression Inventory-II (BDI-II), and 34 patients also had positron emission tomography (PET) imaging with alpha-[11C]methyl-L-tryptophan (AMT). BDI-II scores were correlated with clinical and tumor-related variables, cerebral regional AMT metabolism measured in the non-tumoral hemisphere, and plasma tryptophan metabolite levels. Sixteen patients (27%) had BDI-II scores indicating depression, including 6 with moderate/severe depression. High BDI-II scores were independent of clinical and tumor-related variables except lower Karnofsky Performance Status scores. In patients with recurrent malignant gliomas, depression was associated with shorter survival (hazard ratio: 3.7; p = 0.048). High BDI-II total and somatic subscale scores were associated with higher frontal cortical and thalamic AMT metabolic values measured on PET. In contrast, plasma tryptophan and kynurenine metabolite levels did not correlate with the BDI-II scores. In conclusion, our results confirm previous data that depression affects more than ¼ of patients with primary brain tumors, it is largely independent of tumor characteristics and is associated with shorter survival in patients with recurrent malignant gliomas. On PET imaging, higher tryptophan metabolism in the frontal cortex and thalamus was found in those with brain tumor-associated depression and supports the role of dysregulated tryptophan/kynurenine metabolism in this condition.
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