ArticleCancer cell2024
Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy.
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Article in Cancer cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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80 citing papers in PubMed, 85 citations in OpenAlex.
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- Immune remodeling and myeloid signature in the bone marrow niche of MYCN-driven neuroblastoma.BJC reports · 2026Article
- Integrated Genomic and Proteomic Analysis Reveals T-B Lymphocyte Signatures in the MYCN Driven "Immune Desert" of Specific Neuroblastoma Subtypes.CNS neuroscience & therapeutics · 2026Article
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- 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
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- Single-cell profiling uncovers a hypoxia-vascular-immune axis underlying poor immunotherapy response in acral versus cutaneous melanoma.Journal of translational medicine · 2026Article
- Spatial multi-omics characterization of neuroblastoma reveals ferroptosis-associated metabolic features in high-risk tumors.Genome medicine · 2026Article
- Regulation of natural killer cell infiltration and tumor progression by CMTM6 in gastric cancer.BMC cancer · 2026Article
- Established and Emerging Therapies for High-Risk Neuroblastoma.Paediatric drugs · 2026Review
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- Lactylation-related gene signature as a prognostic biomarker for neuroblastoma: insights into tumor progression and immune modulation.Cell & bioscience · 2026Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Bridging cancer cell-intrinsic driver genes and -extrinsic cell-cell communication with Driver2Comm.PLoS computational biology · 2026Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
48 authors at 11 institutions in 5 countries.
Judith WienkePrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. Electronic address: j.wienke-4@prinsesmaximacentrum.nl.
Lindy L VisserPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Waleed M KholosyPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Kaylee M KellerPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Marta BarisaCancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
Evon PoonDivision of Clinical Studies, The Institute of Cancer Research, London, UK.
Sophie Munnings-TomesCancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
Courtney HimsworthCancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
Elizabeth CaltonDivision of Clinical Studies, The Institute of Cancer Research, London, UK.
Ana RodriguezHoffman-La Roche, Basel, Switzerland.
Ronald BernardiGenentech, A Member of the Roche Group, South San Francisco, CA, USA.
Femke van den HamPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Sander R van HooffPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Yvette A H MatserPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Michelle L TasPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Karin P S LangenbergPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Philip LijnzaadPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Anne L BorstPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Elisa ZappaPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Francisca J BergsmaPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Josephine G M StrijkerPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Bronte M VerhoevenChildhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Shenglin MeiDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Amira KramdiInstitut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
Restuadi RestuadiInfection, Immunity and Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK.
Alvaro Sanchez-BernabeuBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; Netherlands Proteomics Centre, Utrecht University, Utrecht, the Netherlands.
Annelisa M CornelPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
Frank C P HolstegePrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Juliet C GrayCentre for Cancer Immunology, University of Southampton, Southampton, UK.
Godelieve A M TytgatPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Marijn A Scheijde-VermeulenPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Marc H W A WijnenPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Miranda P DierselhuisPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Karin StraathofUniversity College London (UCL) Great Ormond Street Institute of Child Health, London, UK; UCL Cancer Institute, London, UK.
Sam BehjatiWellcome Sanger Institute, Hinxton, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK.
Wei WuBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; Netherlands Proteomics Centre, Utrecht University, Utrecht, the Netherlands; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Department of Pharmacy, National University of Singapore, Singapore, Singapore.
Albert J R HeckBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; Netherlands Proteomics Centre, Utrecht University, Utrecht, the Netherlands.
Jan KosterAmsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Amsterdam, the Netherlands.
Stefan NierkensPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
Isabelle Janoueix-LeroseyInstitut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab, Paris, France; SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie, Paris, France.
Ronald R de KrijgerPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
Ninib BaryawnoChildhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Louis CheslerDivision of Clinical Studies, The Institute of Cancer Research, London, UK.
John AndersonCancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK; Department of Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, England, UK.
Hubert N CaronHoffman-La Roche, Basel, Switzerland.
Thanasis MargaritisPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Max M van NoeselPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Division Imaging & Cancer, University Medical Center Utrecht, Utrecht, the Netherlands.
Jan J MolenaarPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Department of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
Princess Máxima Center · NLInstitute of Cancer Research · GBKarolinska Institutet · SERoche (Switzerland) · CHUniversity College London · GBCRUK Lung Cancer Centre of Excellence · GBGreat Ormond Street Hospital · GBHarvard University · USLa Roche College · USUniversity of Amsterdam · NLUniversity of Southampton · GB
Funding
Cancer Research UK 28278Wellcome Trust
Abstract
Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations. NK cells show reduced cytotoxicity and T cells have a dysfunctional profile. Interaction analysis reveals a vast immunoregulatory network and identifies NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduces neuroblastoma growth, with complete responses (CR) in vivo. Moreover, addition of TIGIT+PD-L1 blockade to standard relapse treatment in a chemotherapy-resistant Th-ALK
Indexed as
B7-H1 AntigenNeuroblastomaChildHumansImmunotherapyNeoplasm Recurrence, LocalReceptors, ImmunologicSequence Analysis, RNAB7-H1 AntigenReceptors, ImmunologicTIGIT protein, humanImmune checkpoint inhibitionimmune evasionimmunotherapyNECTIN2NeuroblastomaPD-1PD-L1Pediatric oncologyTIGITtumor microenvironment
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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.