ArticleJournal for immunotherapy of cancer2023
Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) neutralization counteracts T cell immune evasion in breast cancer.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Development of PROTACs Targeting the Moonlighting Enzyme Nicotinamide Phosphoribosyltransferase (NAMPT) for Breast Cancer Therapy.Journal of medicinal chemistry · 2026Article
- Tumor-Derived CDC37 Inhibits Antigen Cross-Presentation in Dendritic Cells and Impairs Anti-Tumor Immunity in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- eNAMPT Is a Novel DAMP and Therapeutic Target in Human and Murine Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2025Article
- Nicotinamide phosphoribosyltransferase in NADCell death discovery · 2025Review
- The Role of Visfatin in Gastric and Esophageal Cancer: From Biomarker to Therapeutic Target.Cancers · 2025Review
- NEDD4 E3 ligase-catalyzed NAMPT ubiquitination and autophagy activation are essential for pyroptosis-independent NAMPT secretion in human monocytes.Cell communication and signaling : CCS · 2025Article
- The eNAMPT-Integrin α5β1 Axis Mediates Neutrophil-Endothelial Cell Interactions Driving Inflammation in Ulcerative Colitis.Journal of inflammation research · 2025Article
- Molecular Characterization and Clinical Outcomes of Pancreatic Neuroendocrine Neoplasms Harboring PAK4-NAMPT Alterations.JCO oncology advances · 2025Article
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) drives abnormal pericyte-rich vasculature in triple-negative breast cancer.Angiogenesis · 2024Article
- Amphiregulin Upregulation in Visfatin-Stimulated Colorectal Cancer Cells Reduces Sensitivity to 5-Fluororacil Cytotoxicity.Biology · 2024Article
- Biological Functions and Therapeutic Potential of NADCancers · 2024Review
- Robust machine-learning based prognostic index using cytotoxic T lymphocyte evasion genes highlights potential therapeutic targets in colorectal cancer.Cancer cell international · 2024Article
- Pro- and anti-inflammatory cytokines: the hidden keys to autoimmune gastritis therapy.Frontiers in pharmacology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNicotinamide phosphoribosyltransferase (NAMPT) is a key intracellular enzyme that participates in nicotinamide adenine dinucleotide (NAD) homeostasis as well as a released cytokine (eNAMPT) that is elevated in inflammatory conditions and in cancer. In patients with breast cancer, circulating eNAMPT is elevated and its plasma levels correlate with prognosis and staging. In light of this, we investigated the contribution of eNAMPT in triple negative mammary carcinoma progression by investigating the effect of its neutralization via a specific neutralizing monoclonal antibody (C269).
methodsWe used female BALB/c mice injected with 4T1 clone 5 cells and female C57BL6 injected with EO771 cells, evaluating tumoral size, spleen weight and number of metastases. We injected two times a week the anti-eNAMPT neutralizing antibody and we sacrificed the mice after 28 days. Harvested tumors were analyzed by histopathology, flow cytometry, western blot, immunohistochemistry, immunofluorescence and RNA sequencing to define tumor characteristics (isolating tumor infiltrating lymphocytes and tumoral cells) and to investigate the molecular mechanisms behind the observed phenotype. Moreover, we dissected the functional relationship between T cells and tumoral cells using three-dimensional (3D) co-cultures.
resultsThe neutralization of eNAMPT with C269 led to decreased tumor size and reduced number of lung metastases. RNA sequencing and functional assays showed that eNAMPT controlled T-cell response via the programmed death-ligand 1/programmed cell death protein 1 (PD-L1/PD-1) axis and its neutralization led to a restoration of antitumoral immune responses. In particular, eNAMPT neutralization was able to activate CD8
conclusionsThese studies indicate for the first time eNAMPT as a novel immunotherapeutic target for triple negative breast cancer.
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