ArticleBrain, behavior, and immunity2017
Non-tumor cell IDO1 predominantly contributes to enzyme activity and response to CTLA-4/PD-L1 inhibition in mouse glioblastoma.
Article in Brain, behavior, and immunity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas.JCI insight · 2018Trial
- Xenoline-polarized macrophages as an alternative in vitro model of tumor-associated macrophages in glioblastoma.Acta neuropathologica communications · 2025Article
- A pilot study investigating the effect of pembrolizumab on the tumoral immunoprofile of newly diagnosed mullerian cancers.Gynecologic oncology reports · 2025Article
- Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC).Journal of medicinal chemistry · 2025Article
- From neuroinflammation to gliomagenesis: immune drivers of malignant transformation in the CNS.Frontiers in immunology · 2025Review
- Comprehensive analysis of the prognostic value and immunological role of IDO1 gene in pan-cancer.European journal of medical research · 2024Article
- Small-molecule agents for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2024Review
- Bradykinin B1 Receptor Affects Tumor-Associated Macrophage Activity and Glioblastoma Progression.Antioxidants (Basel, Switzerland) · 2023Article
- PPRX-1701, a nanoparticle formulation of 6'-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models.Cell reports. Medicine · 2023Article
- The Conventional Dendritic Cell 1 Subset Primes CD8+ T Cells and Traffics Tumor Antigen to Drive Antitumor Immunity in the Brain.Cancer immunology research · 2023Article
- Endothelial Indoleamine-2,3-Dioxygenase-1 is not Critically Involved in Regulating Antitumor Immunity in the Central Nervous System.International journal of tryptophan research : IJTR · 2023Article
- The signaling function of IDO1 incites the malignant progression of mouse B16 melanoma.Oncoimmunology · 2023Article
- Identification and Characterization of a Novel Indoleamine 2,3-Dioxygenase 1 Protein Degrader for Glioblastoma.Journal of medicinal chemistry · 2022Article
- Evaluation of Novel Inhibitors of Tryptophan Dioxygenases for Enzyme and Species Selectivity Using Engineered Tumour Cell Lines Expressing Either Murine or Human IDO1 or TDO2.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Identification of an IDO1-based immune classifier for survival prediction of upper tract urothelial carcinoma.Cancer science · 2022Article
- Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Immunohistochemical evaluation of immune cell infiltration in canine gliomas.Veterinary pathology · 2021Article
- Computational immune infiltration analysis of pediatric high-grade gliomas (pHGGs) reveals differences in immunosuppression and prognosis by tumor location.Computational and systems oncology · 2021Article
- Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 Expression.Cancers · 2021Article
- Indoleamine 2,3-Dioxygenase 1: A Promising Therapeutic Target in Malignant Tumor.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Glioblastoma (GBM) is the most common malignant brain tumor in adults with a median survival of 14.6months. A contributing factor to GBM aggressiveness is the intratumoral expression of the potently immunosuppressive enzyme, indoleamine 2,3 dioxygenase 1 (IDO1). The enzymatic activity of IDO1 is associated with the conversion of tryptophan into downstream kynurenine (Kyn), which has previously been hypothesized to contribute toward the suppression of tumor immunity. Utilizing the syngeneic, immunocompetent, intracranial GL261 cell GBM model, we previously demonstrated that tumor cell, but not non-tumor cell IDO1, suppresses T cell-mediated brain tumor regression in mice. Paradoxically, we also showed that the survival advantage mediated by immune checkpoint blockade is abrogated by non-tumor cell IDO1 deficiency. Here, we have built on our past observations and confirm the maladaptive role of tumor cell IDO1 in a novel mouse GBM model. We also demonstrate that, non-tumor cells, rather than mouse GBM cells, are the dominant contributor to IDO1-mediated enzyme activity. Finally, we show the novel associations between maximally-effective immune-checkpoint blockade-mediated survival, non-tumor cell IDO1 and intra-GBM Kyn levels. These data suggest for the first time that, GBM cell-mediated immunosuppression is IDO1 enzyme independent, while the survival benefits of immune checkpoint blockade require non-tumor cell IDO1 enzyme activity. Given that current clinical inhibitors vary in their mechanism of action, in terms of targeting IDO1 enzyme activity versus enzyme-independent effects, this work suggests that choosing an appropriate IDO1 pharmacologic will maximize the effectiveness of future immune checkpoint blockade approaches.
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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.