ArticleJournal for immunotherapy of cancer2022
Small extracellular vesicles induce resistance to anti-GD2 immunotherapy unveiling tipifarnib as an adjunct to neuroblastoma immunotherapy.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma.Molecular cancer · 2023Trial
- Single-cell transcriptomic atlas-guided NRG3-ERBB4 axis enhances the efficacy of chemo-immunotherapy during induction phase in high-risk neuroblastoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- IGF2BP1 fosters an immunosuppressive tumor microenvironment in high-risk neuroblastoma, contributing to their resistance to immunotherapy.Oncoimmunology · 2025Article
- Target antigen-displaying extracellular vesicles boost CAR T cell efficacy in cell and mouse models of neuroblastoma.Science translational medicine · 2025Article
- Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy.Current issues in molecular biology · 2025Review
- Anti-PD1 prolongs the response of PI3K and farnesyl transferase inhibition in HRAS- and PIK3CA-mutant head and neck cancers.Neoplasia (New York, N.Y.) · 2025Article
- Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research.Molecular neurobiology · 2025Review
- Effect of Extracellular Vesicles Derived From Tumor Cells on Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Downregulation of ABLIM3 confers to the metastasis of neuroblastoma via regulating the cell adhesion molecules pathway.Computational and structural biotechnology journal · 2024Article
- Review
- Neuroblastoma-A Review of Combination Immunotherapy.International journal of molecular sciences · 2024Review
- Tipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure.Circulation research · 2024Article
- The neuroblastoma tumor microenvironment: From an in-depth characterization towards novel therapies.EJC paediatric oncology · 2024Article
- Review
- Evaluation of a Combinatorial Immunotherapy Regimen That Can Cure Mice Bearing MYCN-Driven High-Risk Neuroblastoma That Resists Current Clinical Therapy.Journal of clinical medicine · 2024Article
- A Group of Highly Secretory miRNAs Correlates with Lymph Node Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma.Biomolecules · 2024Article
- Extracellular vesicles as tools and targets in therapy for diseases.Signal transduction and targeted therapy · 2024Review
- Prospects of anti-GD2 immunotherapy for retinoblastoma.Frontiers in immunology · 2024Review
- Extracellular vesicles in neuroblastoma: role in progression, resistance to therapy and diagnostics.Frontiers in immunology · 2024Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAnti-GD2 monoclonal antibody immunotherapy has significantly improved the overall survival rate for high-risk neuroblastoma patients. However, 40% of patients fail to respond or develop resistance to treatment, and the molecular mechanisms by which this occurs remain poorly understood. Tumor-derived small extracellular vesicles (sEVs) have emerged as critical regulators in modulating the response to immunotherapy. In this study, we investigated the role of neuroblastoma-derived sEVs in promoting resistance to the anti-GD2 monoclonal antibody dinutuximab. Moreover, to determine whether pharmacologic inhibition of sEV secretion sensitizes tumors to dinutuximab treatment, we combined dinutuximab with tipifarnib, a farnesyltransferase inhibitor that inhibits sEV secretion.
methodsWe investigated the role of neuroblastoma-derived sEVs in modulating the response to dinutuximab by utilizing the syngeneic 9464D-GD2 mouse model. The effect of neuroblastoma-derived sEVs in modulating the tumor microenvironment (TME) and host immune system were evaluated by RNA-sequencing and flow cytometry. Importantly, we used this mouse model to investigate the efficacy of tipifarnib in sensitizing neuroblastoma tumors to dinutuximab. The effect of tipifarnib on both the TME and host immune system were assessed by flow cytometry.
resultsWe demonstrated that neuroblastoma-derived sEVs significantly attenuated the efficacy of dinutuximab
conclusionsThese preclinical findings uncover a novel mechanism by which neuroblastoma-derived sEVs modulate the immune system to promote resistance to dinutuximab and suggest that tipifarnib-mediated inhibition of sEV secretion may serve as a viable treatment strategy to enhance the antitumor efficacy of anti-GD2 immunotherapy in high-risk neuroblastoma patients.
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