ArticleCancer immunology research2014
Polyamine-blocking therapy reverses immunosuppression in the tumor microenvironment.
Article in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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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.
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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
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- The Role of the Gut Microbiome in Clinical Outcomes of Colorectal Cancer: A Systematic Review (2020-2025).Oncology research · 2026Pooled it
- Arginine metabolism, polyamine homeostasis and ferroptosis in cancer: Molecular links and therapeutic opportunities (Review).Molecular medicine reports · 2026Review
- Methionine Regulates Antitumour Function of CD8Immunology · 2026Article
- Review
- A direct fluorescence assay for quantitative analysis of ornithine decarboxylase activity and inhibitor screening.The Journal of biological chemistry · 2026Article
- Polyamine Metabolism and the DHPS/eIF5A Hypusination Axis: From Metabolic Reprogramming to a Therapeutic Achilles' Heel in Melanoma.Biomolecules · 2026Review
- The remarkable legacy of the K6/ODC mouse: mechanisms of polyamine-promoted tumorigenesis revealed.Amino acids · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Gut microbiota drives cancer evolution and therapy resistance.Molecular cancer · 2026Review
- The Multi-dimensional Mechanisms and Transformation Prospects of the Intratumoral Microbiota-Arginine Metabolism Axis in Tumor Progression and Immune Regulation.International journal of medical sciences · 2026Review
- Redox-metabolic circuits as a central regulator of T cell-based immunotherapy.Frontiers in immunology · 2026Review
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- Mechanisms and therapeutic strategies for immunotherapy resistance in gastric cancer.Cancer cell international · 2025Review
- Polyamine metabolism in cancer: drivers of immune evasion, ferroptosis and therapy resistance.Expert reviews in molecular medicine · 2025Review
- Mesenchymal stem cell extracellular vesicles ameliorate radiation-caused dry mouth via modulating immune balance and cell metabolism.Stem cell research & therapy · 2025Article
- Methionine regulates antitumor function of CD8bioRxiv : the preprint server for biology · 2025Article
- Immunosuppressant imprecision: multidirectional effects on metabolism and microbiome.Clinical microbiology reviews · 2025Review
- Gut Microbiota and Colorectal Cancer: A Balance Between Risk and Protection.International journal of molecular sciences · 2025Review
- Immunogenic shift of arginine metabolism triggers systemic metabolic and immunological reprogramming to suppress HER2 + breast cancer.Cancer & metabolism · 2025Article
- Antitumor potential of polyamines in cancer.Acta biochimica et biophysica Sinica · 2025Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Correcting T-cell immunosuppression may unleash powerful antitumor responses; however, knowledge about the mechanisms and modifiers that may be targeted to improve therapy remains incomplete. Here, we report that polyamine elevation in cancer, a common metabolic aberration in aggressive lesions, contributes significantly to tumor immunosuppression and that a polyamine depletion strategy can exert antitumor effects that may also promote immunity. A polyamine-blocking therapy (PBT) that combines the well-characterized ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO) with AMXT 1501, a novel inhibitor of the polyamine transport system, blocked tumor growth in immunocompetent mice but not in athymic nude mice lacking T cells. PBT had little effect on the proliferation of epithelial tumor cells, but it increased the number of apoptotic cells. Analysis of CD45(+) tumor immune infiltrates revealed that PBT decreased levels of Gr-1(+)CD11b(+) myeloid suppressor cells and increased CD3(+) T cells. Strikingly, in a model of neoadjuvant therapy, mice administered with PBT one week before surgical resection of engrafted mammary tumors exhibited resistance to subsequent tumor rechallenge. Collectively, our results indicate that therapies targeting polyamine metabolism do not act exclusively as antiproliferative agents, but also act strongly to prevent immune escape by the tumor. PBT may offer a general approach to heighten immune responses in cancer.
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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.