ArticleOncotarget2016
Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Uncovering the research evolution and hotspots of metabolism in renal cell carcinoma over the last decade.Frontiers in oncology · 2025Pooled it
- Metabolic reprogramming-mediated therapeutic resistance in renal cell carcinoma: Mechanisms and targeted intervention strategies.iScience · 2026Review
- Evaluation of the Expression of IDO and PTEN in Human Kidney Cancer.Current issues in molecular biology · 2025Article
- K-Means Clustering of HyperpolarisedCancers · 2025Article
- Mechanism research on inhibition of gastric cancerOpen medicine (Warsaw, Poland) · 2025Article
- Integrated machine learning reveals the role of tryptophan metabolism in clear cell renal cell carcinoma and its association with patient prognosis.Biology direct · 2024Article
- Flavonoids as modulators of metabolic reprogramming in renal cell carcinoma (Review).Oncology reports · 2024Review
- Metabolic alterations in hereditary and sporadic renal cell carcinoma.Nature reviews. Nephrology · 2024Review
- A Review of the Evidence for Tryptophan and the Kynurenine Pathway as a Regulator of Stem Cell Niches in Health and Disease.International journal of tryptophan research : IJTR · 2024Review
- Biological Biomarkers of Response and Resistance to Immune Checkpoint Inhibitors in Renal Cell Carcinoma.Cancers · 2023Review
- Inflammatory Networks in Renal Cell Carcinoma.Cancers · 2023Review
- Comprehensive analyses of A 12-metabolism-associated gene signature and its connection with tumor metastases in clear cell renal cell carcinoma.BMC cancer · 2023Article
- Metabolic reprogramming of clear cell renal cell carcinoma.Frontiers in endocrinology · 2023Review
- Depletion of the mAmerican journal of translational research · 2023Article
- Molecular characterization of renal cell carcinoma tumors from a phase III anti-angiogenic adjuvant therapy trial.Nature communications · 2022Article
- Kynurenine pathway in kidney diseases.Pharmacological reports : PR · 2022Review
- Metabolic reprogramming in renal cancer: Events of a metabolic disease.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Article
- Kynurenines as a Novel Target for the Treatment of Malignancies.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer.Nutrients · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.