Evidence map›Paper›PMID 40508074›Full record

ReviewInternational journal of molecular sciences2025

Targeting Lineage-Specific Functions of NR4A1 for Cancer Immunotherapy.

Jeremy Kleberg, Akhila Nataraj, Yufeng Xiao, Bristy R Podder, Zeng Jin, Tanzia Islam Tithi, Guangrong Zheng, Keiran S M Smalley, Emily K Moser, Stephen Safe and 3 more

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Special Issue "State-of-the-Art Cancer Immunotherapies-2nd Edition".International journal of molecular sciences · 2026
    Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Jeremy KlebergDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.ORCID 0009-0009-7231-7158
Akhila NatarajDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Yufeng XiaoDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.ORCID 0000-0002-2679-0800
Bristy R PodderDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Zeng JinDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Tanzia Islam TithiDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Guangrong ZhengDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.ORCID 0000-0002-8106-6663
Keiran S M SmalleyDepartment of Tumor Microenvironment and Metastasis, Moffitt Cancer Center, Tampa, FL 33612, USA.
Emily K MoserDepartment of Pulmonary, Critical Care and Sleep Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.ORCID 0000-0001-6386-5894
Stephen SafeMolecular & Cellular Oncology Laboratory, Physiology and Pharmacology and of Biochemistry and Biophysics, Texas A&M University Veterinary Medicine & Biomedical Sciences, College Station, TX 77843, USA.ORCID 0000-0002-2115-3060
Chandra K MaharjanDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.ORCID 0000-0003-0673-9888
Ryan KolbDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Weizhou ZhangDepartment of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.ORCID 0000-0002-8236-0346

Funding

Proteolysis-targeting chimera against BCL-XL inhibits breast cancer metastasisR01CA260239 · NCI · UNIVERSITY OF FLORIDA · PI ZHANG, WEIZHOU · 2021 to 2025
$2.5M
Proteolysis targeting chimera against nuclear receptor NR4A1 for melanoma therapyR01CA290792 · NCI · UNIVERSITY OF FLORIDA · PI Keiran Smalley, Weizhou Zhang · 2024 to 2026
$2.0M
Department of Defense BC200100NCI NIH HHS R01 CA260239NCI NIH HHS R01 CA290792NIH/NCI CA269662, CA260239, CA290792
6 · The paper itself

Abstract

Orphan nuclear receptor 4A1 (NR4A1, Nur77) plays a crucial role in regulating immune cell metabolism and function within the tumor microenvironment (TME), thus influencing cancer progression and serving as a potential therapeutic target for cancer immunotherapy. A comprehensive review discussing the multifaceted roles of NR4A1 in immune cells and the exploitation of that knowledge for therapeutic development is lacking in the field. This review explores diverse functions of NR4A1 in tumor-associated immune cells, including T cells, monocytes, natural killer cells, B cells, dendritic cells, macrophages, and neutrophils. NR4A1 contributes to immune regulation by impacting cytokine production, cell differentiation, and immune cell exhaustion. We highlight how NR4A1 in immune cells within the TME may be either a positive (e.g., macrophages in colon cancer) or negative prognostic factor (e.g., T cells in melanoma), depending on the cancer and immune cell context. Additionally, this review also highlights potential therapeutic strategies targeting NR4A1, leading to its inhibition, activation, or degradation to restore immune cell function and enhance anti-tumor immunity. Such therapies could potentially improve patient outcomes by altering immune cell behaviors, blocking intrinsic tumor growth pathways, or via both mechanisms. However, the development of NR4A1-targeted therapies will be dependent on further research to better understand lineage-specific roles of NR4A1 and the underlying mechanisms across different cancer types and immune cells.

Indexed as

ImmunotherapyNeoplasmsNuclear Receptor Subfamily 4, Group A, Member 1AnimalsHumansTumor MicroenvironmentNR4A1 protein, humanNuclear Receptor Subfamily 4, Group A, Member 1cancerimmune cellsimmunotherapiesNR4A1tumor microenvironment

Identifiers

PMID40508074
PMCPMC12155124

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.