Modulation of T cells by tryptophan metabolites in the kynurenine pathway

Stone, T. W.; Williams, Richard O.

doi:10.1016/j.tips.2023.04.006

Cited by 36 publications

(24 citation statements)

References 137 publications

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“…It has been reported that activation of IDO1 in the Kyn pathway leads in addition to the differentiation of naive CD4 + T cells to T lymphocytes regulators (Treg) through the upregulation of forkhead box P3 (FOXP3) (Fig. 2) [9 ▪▪ ]. These immunological effects of IDO1 were also observed in macrophages.…”

Section: Kynurenine Pathway and Immune Dysfunctionmentioning

confidence: 82%

“…Cancer is often associated with changes in immune system function. In this light, the IDO-KYN pathway has been largely studied in the last few years for understanding the cancer-immunity escape mechanism and modulation of T-cell activity [9 ▪▪ ]. For instance, in colorectal cancer increased activity of IDO1 are associated with lower infiltration of immune cells such as lymphocytes T CD3+, CD8+, CD3+ CD8+, and NK CD57+ cells in tumor microenvironment, suggesting an impaired local immune response [7 ▪▪ ].…”

Section: Kynurenine Pathway and Immune Dysfunctionmentioning

confidence: 99%

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Tryptophan metabolism and kynurenine metabolites in cancer: systemic nutritional and metabolic implications

Molfino,

Imbimbo,

Gallicchio

et al. 2024

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review To describe the role of Tryptophan (Trp) metabolism and Kynurenine (Kyn) metabolites in nutritional and metabolic changes in cancer. Recent findings Trp is in part utilized for protein and neurotransmitters biosynthesis, but more than 95% is implicated in Kyn pathways. In this molecular cascade, metabolites are produced with distinct biological activities regulating the immune response and neurotransmission with potential implications in malnutrition/cachexia during cancer. Immune dysfunction is a phenomenon occurring during cancer and malnutrition. Kyn metabolites regulate lymphocytes activity and recent data in animals showed that the inhibition of indoleamine-2,3-dioxygenase (IDO) via 1-methyl-tryptophan determines partial amelioration of inflammation, but no positive effects on the preservation of muscularity were observed. Kynurenines seem to contribute to muscle catabolism via NAD+ biosynthesis and ROS generation. Trp metabolism via the serotonin biosynthesis is involved in appetite control in cancer. Moreover, kynurenines have a role in determining fatigue in conditions associated with inflammation. Summary Trp metabolism has implications in immune and energy balance in cancer. The modulation of Trp and kynurenines have impact on central nervous system mechanisms, including appetite, fatigue, and muscle wasting/cachexia. Research focusing on these clinical implications will open new scenario for therapeutic interventions aimed at counteracting nutritional derangements in cancer.

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Section: Kynurenine Pathway and Immune Dysfunctionmentioning

confidence: 82%

Section: Kynurenine Pathway and Immune Dysfunctionmentioning

confidence: 99%

Tryptophan metabolism and kynurenine metabolites in cancer: systemic nutritional and metabolic implications

Molfino,

Imbimbo,

Gallicchio

et al. 2024

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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show abstract

“…The metabolites above can impede the immune response by stimulating the aromatic hydrocarbon receptor, hence facilitating the advancement of tumors [ 47 ]. Furthermore, T cells have a heightened sensitivity to minimal amounts of TRP, and such low levels of TRP may trigger a response of amino acid deprivation, leading to the demise of T cells and the promotion of immune evasion [ 48 ]. The results of our investigation indicate a direct link between TDO2 and the risk of HCC (OR = 1.99, 95% CI = 1.22–3.25, p -value = 0.006).…”

Section: Discussionmentioning

confidence: 99%

Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis

Ma,

Tang,

Yao

et al. 2024

JPM

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Background: Primary liver cancer (PLC) ranks third in terms of fatality rate among all malignant tumors worldwide. Proteomics and metabolomics have become widely utilized in identifying causes and diagnostic indicators of PLC. Nevertheless, in studies aiming to identify proteins/metabolites that experienced significant changes before PLC, the potential impact of reverse causation and confounding variables still needs to be fully addressed. Methods: This study thoroughly investigated the causal relationship between 4719 blood proteins, 21 amino acids, and the risk of PLC using the Mendelian randomization (MR) method. In addition, through a comprehensive analysis of the TCGA-LIHC cohort and GEO databases, we evaluated the differentially expressed genes (DEGs) related to serine metabolism in diagnosing and predicting the prognosis of patients with PLC. Results: A total of 63 proteins have been identified as connected to the risk of PLC. Additionally, there has been confirmation of a positive cause–effect between PLC and the concentration of serine. The integration of findings from both MR analyses determined that the protein associated with PLC risk exhibited a significant correlation with serine metabolism. Upon careful analysis of the TCGA-LIHC cohort, it was found that eight DEGs are linked to serine metabolism. After thoroughly validating the GEO database, two DEGs, TDO2 and MICB, emerged as potential biomarkers for diagnosing PLC. Conclusions: Two proteins involved in serine metabolism, MICB and TDO2, are causally linked to the risk of PLC and could potentially be used as diagnostic indicators.

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“…In most cases, AhR activation results in the alteration of the tumor-immune cell interactions, with suppression of anti-tumor functions and induction of tumor-permissive or tumor-promoting immune landscapes, as AhR has been shown to regulate the differentiation of multiple cell types in both the innate and the adaptive immune response compartments. Several recent reviews have extensively described the role of AhR in the regulation of the immune system during cancer progression (85)(86)(87)(88); thus, here we will briefly summarize some of the recent key findings.…”

Section: Ahr and Immunitymentioning

confidence: 99%

The aryl hydrocarbon receptor as a tumor modulator: mechanisms to therapy

Chaudhry,

Bianchi-Smiraglia

2024

Front. Oncol.

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The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is widely recognized to play important, but complex, modulatory roles in a variety of tumor types. In this review, we comprehensively summarize the increasingly controversial role of AhR as a tumor regulator and the mechanisms by which it alters tumor progression based on the cancer cell type. Finally, we discuss new and emerging strategies to therapeutically modulate AhR, focusing on novel agents that hold promise in current human clinical trials as well as existing FDA-approved drugs that could potentially be repurposed for cancer therapy.

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Modulation of T cells by tryptophan metabolites in the kynurenine pathway

Cited by 36 publications

References 137 publications

Tryptophan metabolism and kynurenine metabolites in cancer: systemic nutritional and metabolic implications

Tryptophan metabolism and kynurenine metabolites in cancer: systemic nutritional and metabolic implications

Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis

The aryl hydrocarbon receptor as a tumor modulator: mechanisms to therapy

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