ArticleOncotarget2016
Indoleamine 2,3-dioxygenase regulates anti-tumor immunity in lung cancer by metabolic reprogramming of immune cells in the tumor microenvironment.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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.
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Who cites it
56 citing papers in PubMed, 83 citations in OpenAlex.
- From guardians to traitors: molecular mechanisms of tumor-induced T cell betrayal.Molecular cancer · 2026Review
- Neutrophils in non-small cell lung cancer and immunotherapy with PD-1/PD-L1 inhibitors.Journal of translational medicine · 2025Review
- Pyruvate Kinase M2-Responsive Release of Paclitaxel and Indoleamine 2,3-Dioxygenase Inhibitor for Immuno-Chemotherapy of Nonsmall Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cellular senescence in colorectal cancer: its occurrence, effect and therapy.Frontiers in oncology · 2025Review
- Metabolic reprogramming of tumor-associated neutrophils in tumor treatment and therapeutic resistance.Frontiers in cell and developmental biology · 2025Review
- Review
- Optimizing CD8Experimental hematology & oncology · 2024Review
- Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion.Experimental hematology & oncology · 2024Review
- Review
- Targeting amino acid-metabolizing enzymes for cancer immunotherapy.Frontiers in immunology · 2024Review
- Tryptophan Metabolism in Obesity: The Indoleamine 2,3-Dioxygenase-1 Activity and Therapeutic Options.Advances in experimental medicine and biology · 2024Review
- Immunoregulatory paracrine effect of mesenchymal stem cells and mechanism in the treatment of osteoarthritis.Frontiers in cell and developmental biology · 2024Review
- Upregulation of Indoleamine 2,3-Dioxygenase 1 in Tumor Cells and Tertiary Lymphoid Structures is a Hallmark of Inflamed Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Regulation of T cells by myeloid-derived suppressor cells: emerging immunosuppressor in lung cancer.Discover oncology · 2023Review
- The High-Risk Human Papillomavirus Type Influences the Tissue Microenvironment in Cervical Intraepithelial Neoplasia Grade 2.Viruses · 2023Article
- Cellular and molecular features related to exceptional therapy response and extreme long-term survival in glioblastoma.Cancer medicine · 2023Review
- Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers.Molecular cancer · 2023Review
- Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment.Frontiers in oncology · 2023Review
- Nanoparticles overcome adaptive immune resistance and enhance immunotherapyFrontiers in pharmacology · 2023Review
- Indoleamine 2,3-dioxygenase (IDO) inhibitors and cancer immunotherapy.Cancer treatment reviews · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses and survival; however, exact mechanisms remain incompletely understood. We previously reported that a combination therapy of gemcitabine and a superoxide dismutase mimetic promotes anti-tumor immunity in a mouse model of lung cancer by inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and extending survival. Here, we show that combination therapy targets IDO signaling, specifically in MDSCs, tumor cells, and CD8+ T cells infiltrating the TME. Deficiency of IDO caused significant reduction in tumor burden, tumor-infiltrating MDSCs, GM-CSF, MDSC survival and infiltration of programmed death receptor-1 (PD-1)-expressing CD8+ T cells compared to controls. IDO-/- MDSCs downregulated nutrient-sensing AMP-activated protein kinase (AMPK) activity, but IDO-/- CD8+ T cells showed AMPK activation associated with enhanced effector function. Our studies provide proof-of-concept for the efficacy of this combination therapy in inhibiting IDO and T cell exhaustion in a syngeneic model of lung cancer and provide mechanistic insights for IDO-dependent metabolic reprogramming of MDSCs that reduces T cell exhaustion and regulates anti-tumor immunity.
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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.