ArticleJournal for immunotherapy of cancer2019
Combined innate and adaptive immunotherapy overcomes resistance of immunologically cold syngeneic murine neuroblastoma to checkpoint inhibition.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Can Radiotherapy Empower the Host Immune System to Counterattack Neoplastic Cells? A Systematic Review on Tumor Microenvironment Radiomodulation.Current oncology (Toronto, Ont.) · 2022Pooled it
- Bispecific GD2xB7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma.bioRxiv : the preprint server for biology · 2026Article
- Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis.Science advances · 2026Article
- Divergent role of CD8 T cells with distinct metabolic phenotypes during curative radio-immunotherapy in hot versus cold tumors.bioRxiv : the preprint server for biology · 2026Article
- Irinotecan Modulates Immune Checkpoints in Neuroblastoma.ImmunoTargets and therapy · 2026Article
- IGF2BP1 fosters an immunosuppressive tumor microenvironment in high-risk neuroblastoma, contributing to their resistance to immunotherapy.Oncoimmunology · 2025Article
- Research progress in the construction and application of immunotherapy resistance models.Cancer immunology, immunotherapy : CII · 2025Review
- Perioperative poly(I:C) reverses accelerated tumor growth after surgery in neuroblastoma.ImmunoHorizons · 2025Article
- High-risk neuroblastoma as a model for immunotherapy of non-immunogenic cancers: where might we be in 20 years?Journal for immunotherapy of cancer · 2025Review
- Reprogramming the neuroblastoma tumor immune microenvironment to enhance GPC2 CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Phase I Study ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Theranostics for Neuroblastoma: Making Molecular Radiotherapy Work Better.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Radionuclide-Dependent Stimulation of Antitumor Immunity in GD2-Targeted Radiopharmaceutical Therapy Combined with Immune Checkpoint Inhibitors.Radiation (Multidisciplinary Digital Publishing Institute) · 2025Article
- Copper chelation redirects neutrophil function to enhance anti-GD2 antibody therapy in neuroblastoma.Nature communications · 2024Article
- Natural killer cells in neuroblastoma: immunological insights and therapeutic perspectives.Cancer metastasis reviews · 2024Review
- Epigenetic regulation of cell state by H2AFY governs immunogenicity in high-risk neuroblastoma.The Journal of clinical investigation · 2024Article
- Molecular profiling of core immune-escape genes highlights TNFAIP3 as an immune-related prognostic biomarker in neuroblastoma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- CAR T-cell-mediated delivery of bispecific innate immune cell engagers for neuroblastoma.Nature communications · 2024Article
- Enhancing IgA-mediated neutrophil cytotoxicity against neuroblastoma by CD47 blockade.Journal for immunotherapy of cancer · 2024Article
- Critical role of the gut microbiota in immune responses and cancer immunotherapy.Journal of hematology & oncology · 2024Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundUnlike some adult cancers, most pediatric cancers are considered immunologically cold and generally less responsive to immunotherapy. While immunotherapy has already been incorporated into standard of care treatment for pediatric patients with high-risk neuroblastoma, overall survival remains poor. In a mouse melanoma model, we found that radiation and tumor-specific immunocytokine generate an in situ vaccination response in syngeneic mice bearing large tumors. Here, we tested whether a novel immunotherapeutic approach utilizing radiation and immunocytokine together with innate immune stimulation could generate a potent antitumor response with immunologic memory against syngeneic murine neuroblastoma.
methodsMice bearing disialoganglioside (GD2)-expressing neuroblastoma tumors (either NXS2 or 9464D-GD2) were treated with radiation and immunotherapy (including anti-GD2 immunocytokine with or without anti-CTLA-4, CpG and anti-CD40 monoclonal antibody). Tumor growth, animal survival and immune cell infiltrate were analyzed in the tumor microenvironment in response to various treatment regimens.
resultsNXS2 had a moderate tumor mutation burden (TMB) while N-MYC driven 9464D-GD2 had a low TMB, therefore the latter served as a better model for high-risk neuroblastoma (an immunologically cold tumor). Radiation and immunocytokine induced a potent in situ vaccination response against NXS2 tumors, but not in the 9464D-GD2 tumor model. Addition of checkpoint blockade with anti-CTLA-4 was not effective alone against 9464D-GD2 tumors; inclusion of CpG and anti-CD40 achieved a potent antitumor response with decreased T regulatory cells within the tumors and induction of immunologic memory.
conclusionsThese data suggest that a combined innate and adaptive immunotherapeutic approach can be effective against immunologically cold syngeneic murine neuroblastoma. Further testing is needed to determine how these concepts might translate into development of more effective immunotherapeutic approaches for the treatment of clinically high-risk neuroblastoma.
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Registered trials
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