ArticleJournal of translational medicine2012
Indoleamine 2,3-dioxygenase 1 (IDO1) activity correlates with immune system abnormalities in multiple myeloma.
Article in Journal of translational medicine, 2012. 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, 67 citations in OpenAlex.
- Targeting Overexpressed IDO in Stromal Cells as a Potential Therapeutic Strategy in Multiple Myeloma.Cancer science · 2026Article
- Metabolic reprogramming in tumor-associated cells of hematologic malignancies: mechanisms, crosstalk networks, and therapeutic implications in the tumor microenvironment.Frontiers in immunology · 2026Review
- CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization.Cell communication and signaling : CCS · 2025Review
- Functions and mechanisms of lncRNAs in immune escape and their application in immunotherapy for colorectal cancer.Journal of translational medicine · 2025Review
- Pre-diagnostic plasma inflammatory proteins and risk of hepatocellular carcinoma in three population-based cohort studies from the United States and the United Kingdom.International journal of cancer · 2024Article
- Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.International journal of molecular sciences · 2024Review
- Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality.The Journal of clinical investigation · 2024Observational
- Tumor-Associated Macrophages in Multiple Myeloma: Key Role in Disease Biology and Potential Therapeutic Implications.Current oncology (Toronto, Ont.) · 2023Review
- Therapeutic strategies to enhance immune response induced by multiple myeloma cells.Frontiers in immunology · 2023Review
- Normalization of the Immunological Microenvironment and Sustained Minimal Residual Disease Negativity: Do We Need Both for Long-Term Control of Multiple Myeloma?International journal of molecular sciences · 2022Review
- Treating Multiple Myeloma in the Context of the Bone Marrow Microenvironment.Current oncology (Toronto, Ont.) · 2022Review
- Tumor-associated macrophages in multiple myeloma: advances in biology and therapy.Journal for immunotherapy of cancer · 2022Review
- IDO2 rs10109853 polymorphism affects the susceptibility to multiple myeloma.Clinical and experimental medicine · 2021Article
- Immune System Alterations in Multiple Myeloma: Molecular Mechanisms and Therapeutic Strategies to Reverse Immunosuppression.Cancers · 2021Review
- Review
- The HGF/c-MET axis as a potential target to overcome survival signals and improve therapeutic efficacy in multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Immune-based therapies in the management of multiple myeloma.Blood cancer journal · 2020Review
- Autocrine HGF/c-Met signaling pathway confers aggressiveness in lymph node adult T-cell leukemia/lymphoma.Oncogene · 2020Article
- Deregulation of Adaptive T Cell Immunity in Multiple Myeloma: Insights Into Mechanisms and Therapeutic Opportunities.Frontiers in oncology · 2020Review
- IDO1 depletion induces an anti-inflammatory response in macrophages in mice with chronic viral myocarditis.Cell cycle (Georgetown, Tex.) · 2019Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultiple myeloma (MM) is a plasma cell malignancy with a multifaceted immune dysfunction. Indoleamine 2,3-dioxygenase 1 (IDO1) degrades tryptophan into kynurenine (KYN), which inhibits effector T cells and promote regulatory T-cell (Treg) differentiation. It is presently unknown whether MM cells express IDO1 and whether IDO1 activity correlates with immune system impairment.
methodsWe investigated IDO1 expression in 25 consecutive patients with symptomatic MM and in 7 patients with either monoclonal gammopathy of unknown significance (MGUS; n=3) or smoldering MM (SMM; n=4). IDO1-driven tryptophan breakdown was correlated with the release of hepatocyte growth factor (HGF) and with the frequency of Treg cells and NY-ESO-1-specific CD8(+) T cells.
resultsKYN was increased in 75% of patients with symptomatic MM and correlated with the expansion of CD4(+)CD25(+)FoxP3(+) Treg cells and the contraction of NY-ESO-1-specific CD8(+) T cells. In vitro, primary MM cells promoted the differentiation of allogeneic CD4(+) T cells into bona fide CD4(+)CD25(hi)FoxP3(hi) Treg cells and suppressed IFN-γ/IL-2 secretion, while preserving IL-4 and IL-10 production. Both Treg expansion and inhibition of Th1 differentiation by MM cells were reverted, at least in part, by D,L-1-methyl-tryptophan, a chemical inhibitor of IDO. Notably, HGF levels were higher within the BM microenvironment of patients with IDO(+) myeloma disease compared with patients having IDO(-) MM. Mechanistically, the antagonism of MET receptor for HGF with SU11274, a MET inhibitor, prevented HGF-induced AKT phosphorylation in MM cells and translated into reduced IDO protein levels and functional activity.
conclusionsThese data suggest that IDO1 expression may contribute to immune suppression in patients with MM and possibly other HGF-producing cancers.
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