ArticleThe Journal of clinical investigation2022
Inhibiting the biogenesis of myeloid-derived suppressor cells enhances immunotherapy efficacy against mammary tumor progression.
Article in The Journal of clinical investigation, 2022. 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, 45 citations in OpenAlex.
- The Diagnostic and Prognostic Value of miR-155 in Cancers: An Updated Meta-analysis.Molecular diagnosis & therapy · 2023Pooled it
- Obesity Promotes Lung Carcinogenesis Through Airway Immune Dysfunction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Tirzepatide mitigates atherosclerosis progression and modulates oxLDL-mediated proatherogenic effects in macrophages: evidence for M1/M2 homeostasis restoration.Archives of pharmacal research · 2026Article
- Nintedanib enhances the antitumor efficacy of pd-1 blockade, potentially through inhibition of myeloid-derived suppressor cells and cancer-associated fibroblasts.Cancer immunology, immunotherapy : CII · 2026Article
- Epigenetic regulation of EZH2 by ncRNAs: mechanisms and oncogenic implications.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- BiTE-secreting T cells rationally combine with PD-1 blockade and vaccine boosting to reshape antitumor immunity in ovarian cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- B7-H3 (CD276) regulates myeloid-derived suppressor cell differentiation in pulmonary fibrosis.Frontiers in immunology · 2026Article
- KIRA6 restrains the generation of myeloid-derived suppressor cells and overcomes resistance to anti-PD-1 therapy.Cell death & disease · 2025Article
- An immunometabolic prodrug strategy overcomes DHODH inhibitor resistance in refractory melanoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Dihydroorotate dehydrogenase inhibition activates STING pathway and pyroptosis to enhance NK cell-dependent tumor immunotherapy.Molecular biomedicine · 2025Article
- Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer.Breast cancer research : BCR · 2025Article
- Tumor microenvironment response to neoadjuvant therapy in breast cancer: insights from single-cell and spatial omics.Medical oncology (Northwood, London, England) · 2025Review
- A CXCR4 partial agonist improves immunotherapy by targeting immunosuppressive neutrophils and cancer-driven granulopoiesis.Cancer cell · 2025Article
- DHODH modulates immune evasion of cancer cells via CDP-Choline dependent regulation of phospholipid metabolism and ferroptosis.Nature communications · 2025Article
- Article
- Tumor Microenvironment Dynamics of Triple-Negative Breast Cancer Under Radiation Therapy.International journal of molecular sciences · 2025Review
- Exosomes derived from natural killer cells: transforming immunotherapy for aggressive breast cancer.Medical oncology (Northwood, London, England) · 2025Review
- Numb family proteins play roles in Desmin and Vimentin localization at the Z-disc.Journal of muscle research and cell motility · 2025Article
- Activated B cells modulate the maturation of MDSCs via CD36-dependent MHC-II transfer to orchestrate CD4International journal of biological sciences · 2025Article
- Emerging Role of MDSCS as Novel Biomarkers and Therapeutic Targets for Cancer Immunotherapy.ImmunoTargets and therapy · 2025Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
While immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape in oncology, they are effective in select subsets of patients. Efficacy may be limited by tumor-driven immune suppression, of which 1 key mechanism is the development of myeloid-derived suppressor cells (MDSCs). A fundamental gap in MDSC therapeutics is the lack of approaches that target MDSC biogenesis. We hypothesized that targeting MDSC biogenesis would mitigate MDSC burden and bolster tumor responses to ICIs. We tested a class of agents, dihydroorotate dehydrogenase (DHODH) inhibitors, that have been previously shown to restore the terminal differentiation of leukemic myeloid progenitors. DHODH inhibitors have demonstrated preclinical safety and are under clinical study for hematologic malignancies. Using mouse models of mammary cancer that elicit robust MDSC responses, we demonstrated that the DHODH inhibitor brequinar (a) suppressed MDSC production from early-stage myeloid progenitors, which was accompanied by enhanced myeloid maturation; (b) augmented the antitumor and antimetastatic activities of programmed cell death 1-based (PD-1-based) ICI therapy in ICI-resistant mammary cancer models; and (c) acted in concert with PD-1 blockade through modulation of MDSC and CD8+ T cell responses. Moreover, brequinar facilitated myeloid maturation and inhibited immune-suppressive features in human bone marrow culture systems. These findings advance the concept of MDSC differentiation therapy in immuno-oncology.
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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.