ArticleCancer immunology, immunotherapy : CII2023
Bis-indole-derived NR4A1 antagonists inhibit colon tumor and splenic growth and T-cell exhaustion.
Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 20 citations in OpenAlex.
- Nur77 agonism invigorates Natural Killer cell immunity against hepatocellular carcinoma.Nature communications · 2026Article
- Article
- NR4A1 limits CD8Research square · 2026Article
- NR4A1 limits CD8⁺ T Cell effector responses and protection in tuberculosis.bioRxiv : the preprint server for biology · 2026Article
- A Commentary on Dual Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 Ligands.Journal of cellular immunology · 2026Article
- Age-stratified analysis of therapeutic, immune, and glycosylation gene expression in colorectal cancer using machine learning.Scientific reports · 2025Article
- NR4A nuclear receptor expression in human macrophages mediates apoptosis and controls Mycobacterium tuberculosis growth.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Orphan nuclear receptor 4A1 (NR4A1) and NR4A2 are endogenous regulators of CD71 and their ligands induce ferroptosis in breast cancer.Cell death & disease · 2025Article
- Dual Targeting of Orphan Nuclear Receptors NR4A1 and NR4A2 for Nonhormonal Endometriosis Therapy.Endocrinology · 2025Article
- Targeting Lineage-Specific Functions of NR4A1 for Cancer Immunotherapy.International journal of molecular sciences · 2025Review
- Expression of Prooncogenic Nuclear Receptor 4A (NR4A)-Regulated Genes β1-Integrin and G9a Inhibited by Dual NR4A1/2 Ligands.International journal of molecular sciences · 2025Article
- Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis.Chemical research in toxicology · 2025Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Dual nuclear receptor 4A1 (NR4A1/NR4A2) ligands inhibit glioblastoma growth and target TWIST1.Molecular pharmacology · 2025Article
- Article
- Targeting the nuclear orphan receptor NR4A1: a key target in lung cancer progression and therapeutic resistance.Frontiers in oncology · 2025Review
- Deciphering the mechanistic roles of ADARs in cancer pathogenesis, tumor immune evasion, and drug resistance.Frontiers in immunology · 2025Review
- Development of a Competitive Nutrient-Based T-Cell Immunotherapy Designed to Block the Adaptive Warburg Effect in Acute Myeloid Leukemia.Biomedicines · 2024Article
- Molecular Mechanisms of Tumorgenesis and Metastasis of Long Non-coding RNA (lncRNA) NEAT1 in Human Solid Tumors; An Update.Cell biochemistry and biophysics · 2024Review
- Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia.International journal of molecular sciences · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
There is evidence that the orphan nuclear receptor 4A1 (NR4A1, Nur77) is overexpressed in exhausted CD8 + T cells and regulates PD-L1 in tumors. This study investigated the effects of potent bis-indole-derived NR4A1 antagonists on reversing T-cell exhaustion and downregulating PD-L1 in colon tumors/cells. NR4A1 antagonists inhibited colon tumor growth and downregulated expression of PD-L1 in mouse colon MC-38-derived tumors and cells. TILs from MC-38 cell-derived colon tumors and splenic lymphocytes exhibited high levels of the T-cell exhaustion markers including PD-1, 2B4, TIM3+ and TIGIT and similar results were observed in the spleen, and these were inhibited by NR4A1 antagonists. In addition, treatment with NR4A1 antagonists induced cytokine activation markers interferon γ, granzyme B and perforin mRNAs and decreased TOX, TOX2 and NFAT in TIL-derived CD8 + T cells. Thus, NR4A1 antagonists decrease NR4A1-dependent pro-oncogenic activity and PD-L1 expression in colon tumors and inhibit NR4A1-dependent T-cell exhaustion in TILs and spleen and represent a novel class of mechanism-based drugs that enhance immune surveillance in tumors.
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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.