Kynureninase Promotes Immunosuppression and Predicts Survival in Glioma Patients: In Silico Data Analyses of the Chinese Glioma Genome Atlas (CGGA) and of the Cancer Genome Atlas (TCGA)

Cruz, Gonzalo; Cruz, Verónica Pérez de la; Cossio, Javier Navarro; Cervantes, Gustavo Ignacio Vázquez; Salazar, Alelí; Morales, Mario Orozco; Pineda, Benjamín

doi:10.3390/ph16030369

Cited by 2 publications

(2 citation statements)

References 78 publications

(89 reference statements)

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“…Considering recent findings by our group as well as others ( 22 , 23 , 78 , 79 , 81 , 83 , 157 ), targeting of KYNU for anti-cancer treatment and reversal of immune suppression warrants investigation. To date, a few kynurenine analogues have been developed that selectively inhibit KYNU enzymatic activity ( 158 ).…”

Section: Targeting the Kynurenine Pathway For Anti-cancer Treatmentmentioning

confidence: 80%

The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer

León-Letelier,

Dou,

Vykoukal

et al. 2023

Front. Oncol.

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The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) highlight the known biological functions of key enzymes in the KP, and 2) provide a comprehensive overview of existing and emerging therapies aimed at targeting discrete enzymes in the KP for anti-cancer treatment.

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Section: Targeting the Kynurenine Pathway For Anti-cancer Treatmentmentioning

confidence: 80%

The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer

León-Letelier,

Dou,

Vykoukal

et al. 2023

Front. Oncol.

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“… 60 , 353 - 355 Its overexpression is correlated with tumour grade and poor prognosis in triple-negative breast cancer and brain tumours, with TDO2 inhibition suggested as a therapeutic target in oesophageal cancer. 353 Upregulation of other downstream KP enzymes including AFMID, 356 KMO, 357 - 360 KYNU 361 and QPRT, 362 - 364 has also been observed in various cancers. KYNU facilitates tumour growth by catabolising 3-HK to 3-HAA, with 3-HAA inhibiting ferroptotic death of tumour cells, a process that can be negated by HAAO-mediated catabolic depletion of 3-HAA.…”

Section: Stem Cellsmentioning

confidence: 99%

A Review of the Evidence for Tryptophan and the Kynurenine Pathway as a Regulator of Stem Cell Niches in Health and Disease

Summers,

Thomas Broome,

Pang

et al. 2024

Int J�Tryptophan�Res

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Stem cells are ubiquitously found in various tissues and organs in the body, and underpin the body’s ability to repair itself following injury or disease initiation, though repair can sometimes be compromised. Understanding how stem cells are produced, and functional signaling systems between different niches is critical to understanding the potential use of stem cells in regenerative medicine. In this context, this review considers kynurenine pathway (KP) metabolism in multipotent adult progenitor cells, embryonic, haematopoietic, neural, cancer, cardiac and induced pluripotent stem cells, endothelial progenitor cells, and mesenchymal stromal cells. The KP is the major enzymatic pathway for sequentially catabolising the essential amino acid tryptophan (TRP), resulting in key metabolites including kynurenine, kynurenic acid, and quinolinic acid (QUIN). QUIN metabolism transitions into the adjoining de novo pathway for nicotinamide adenine dinucleotide (NAD) production, a critical cofactor in many fundamental cellular biochemical pathways. How stem cells uptake and utilise TRP varies between different species and stem cell types, because of their expression of transporters and responses to inflammatory cytokines. Several KP metabolites are physiologically active, with either beneficial or detrimental outcomes, and evidence of this is presented relating to several stem cell types, which is important as they may exert a significant impact on surrounding differentiated cells, particularly if they metabolise or secrete metabolites differently. Interferon-gamma (IFN-γ) in mesenchymal stromal cells, for instance, highly upregulates rate-limiting enzyme indoleamine-2,3-dioxygenase (IDO-1), initiating TRP depletion and production of metabolites including kynurenine/kynurenic acid, known agonists of the Aryl hydrocarbon receptor (AhR) transcription factor. AhR transcriptionally regulates an immunosuppressive phenotype, making them attractive for regenerative therapy. We also draw attention to important gaps in knowledge for future studies, which will underpin future application for stem cell-based cellular therapies or optimising drugs which can modulate the KP in innate stem cell populations, for disease treatment.

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Kynureninase Promotes Immunosuppression and Predicts Survival in Glioma Patients: In Silico Data Analyses of the Chinese Glioma Genome Atlas (CGGA) and of the Cancer Genome Atlas (TCGA)

Cited by 2 publications

References 78 publications

The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer

The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer

A Review of the Evidence for Tryptophan and the Kynurenine Pathway as a Regulator of Stem Cell Niches in Health and Disease

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