ArticleCancer research2015
Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed.
- Targeting the arginine metabolic brake enhances immunotherapy for leukaemia.International journal of cancer · 2019Trial
- Loss of Arginase 2 Promotes Lung Metastasis in immune-competent hosts via Nitric Oxide Synthase 2-Dependent Th17 Response.bioRxiv : the preprint server for biology · 2026Article
- Metabolic reprogramming of CAR-T cells: a multi-pronged strategy to conquer the immunosuppressive tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Advancing Small-Molecule Immunotherapy Through Polymeric Micelle Delivery.Pharmaceutics · 2026Review
- Deciphering the MYCN-driven metabolic microenvironment of neuroblastoma.Trends in molecular medicine · 2026Review
- Neutrophil Plasticity and NETosis in Tumour Microenvironment: Tumour Evolution and Therapy Resistance.Journal of immunology research · 2026Review
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- Myeloid derived suppressor cells in neuroblastoma: mechanisms of immune evasion and therapeutic opportunities.Frontiers in immunology · 2026Review
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
- Identification of SLC7A1 as a potential therapeutic target for high-grade meningioma.Cell death discovery · 2025Article
- Arginine depletion potentiates standard-of-care chemo-immunotherapy in preclinical models of high-risk neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Interplay Between the Epigenome, the Microenvironment, and the Immune System in Neuroblastoma.Cancers · 2025Review
- Blocking MIF secretion enhances CAR T-cell efficacy against neuroblastoma.European journal of cancer (Oxford, England : 1990) · 2025Article
- Arginine: at the crossroads of nitrogen metabolism.The EMBO journal · 2025Review
- T cells in the microenvironment of solid pediatric tumors: the case of neuroblastoma.Frontiers in immunology · 2025Review
- Natural killer cells in neuroblastoma: immunological insights and therapeutic perspectives.Cancer metastasis reviews · 2024Review
- Review
- The miR-29 family facilitates the activation of NK-cell immune responses by targeting the B7-H3 immune checkpoint in neuroblastoma.Cell death & disease · 2024Article
- Review
- Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy.Oncology research · 2024Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
Abstract
Neuroblastoma is the most common extracranial solid tumor of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumor cells suppress T-cell proliferation through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine-deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34(+) progenitor proliferation. Finally, we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1-specific T-cell receptor and GD2-specific chimeric antigen receptor-engineered T-cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for patients with neuroblastoma. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumor and blood that leads to impaired immunosurveillance and suboptimal efficacy of immunotherapeutic approaches.
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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.