ArticleJournal of translational medicine2019
Medulloblastoma rendered susceptible to NK-cell attack by TGFβ neutralization.
Article in Journal of translational medicine, 2019. 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, 44 citations in OpenAlex.
- The promise of immunotherapy for central nervous system tumours.Nature reviews. Immunology · 2026Review
- Update of NK cell therapy in pediatric brain tumors.Journal of neuro-oncology · 2026Review
- FCGBP promotes malignant phenotypes of glioblastoma cells via activation of the TGF-β1 signaling pathway.American journal of translational research · 2026Article
- Decoding the immune microenvironment: precision immunotherapy for medulloblastoma subtypes.Frontiers in immunology · 2026Review
- Identification of a conserved subset of cold tumors responsive to immune checkpoint blockade.Journal for immunotherapy of cancer · 2025Article
- Cancer immunotherapy insights: key takeaways from the ADSCC bone marrow and cellular therapy congress 2024.Frontiers in immunology · 2025Review
- Review
- Exploring the Molecular Complexity of Medulloblastoma: Implications for Diagnosis and Treatment.Diagnostics (Basel, Switzerland) · 2023Review
- Immunobiology and Cytokine Modulation of the Pediatric Brain Tumor Microenvironment: A Scoping Review.Cancers · 2023Article
- Advanced T and Natural Killer Cell Therapy for Glioblastoma.Journal of Korean Neurosurgical Society · 2023Article
- Pediatric Brain Tumours: Lessons from the Immune Microenvironment.Current oncology (Toronto, Ont.) · 2023Review
- Cellular immunotherapy for medulloblastoma.Neuro-oncology · 2023Review
- Advances in NK cell therapy for brain tumors.NPJ precision oncology · 2023Review
- Epigenetics and immune cells in medulloblastoma.Frontiers in genetics · 2023Review
- Co-transducing B7H3 CAR-NK cells with the DNR preserves their cytolytic function against GBM in the presence of exogenous TGF-β.Molecular therapy. Methods & clinical development · 2022Article
- Clinical and Molecular Features in Medulloblastomas Subtypes in Children in a Cohort in Taiwan.Cancers · 2022Article
- Article
- Coming in from the cold: overcoming the hostile immune microenvironment of medulloblastoma.Genes & development · 2022Review
- NK cells in the brain: implications for brain tumor development and therapy.Trends in molecular medicine · 2022Review
- Review
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMedulloblastoma (MB), the most common pediatric brain cancer, presents with a poor prognosis in a subset of patients with high risk disease, or at recurrence, where current therapies are ineffective. Cord blood (CB) natural killer (NK) cells may be promising off-the-shelf effector cells for immunotherapy due to their recognition of malignant cells without the need for a known target, ready availability from multiple banks, and their potential to expand exponentially. However, they are currently limited by immune suppressive cytokines secreted in the MB tumor microenvironment including Transforming Growth Factor β (TGF-β). Here, we address this challenge in in vitro models of MB.
methodsCB-derived NK cells were modified to express a dominant negative TGF-β receptor II (DNRII) using retroviral transduction. The ability of transduced CB cells to maintain function in the presence of medulloblastoma-conditioned media was then assessed.
resultsWe observed that the cytotoxic ability of nontransduced CB-NK cells was reduced in the presence of TGF-β-rich, medulloblastoma-conditioned media (21.21 ± 1.19% killing at E:T 5:1 in the absence vs. 14.98 ± 2.11% in the presence of medulloblastoma-conditioned media, n = 8, p = 0.02), but was unaffected in CB-derived DNRII-transduced NK cells (21.11 ± 1.84% killing at E:T 5:1 in the absence vs. 21.81 ± 3.37 in the presence of medulloblastoma-conditioned media, n = 8, p = 0.85. We also observed decreased expression of CCR2 in untransduced NK cells (mean CCR2 MFI 826 ± 117 in untransduced NK + MB supernatant from mean CCR2 MFI 1639.29 ± 215 in no MB supernatant, n = 7, p = 0.0156), but not in the transduced cells. Finally, we observed that CB-derived DNRII-transduced NK cells may protect surrounding immune cells by providing a cytokine sink for TGF-β (decreased TGF-β levels of 610 ± 265 pg/mL in CB-derived DNRII-transduced NK cells vs. 1817 ± 342 pg/mL in untransduced cells; p = 0.008).
conclusionsCB NK cells expressing a TGF-β DNRII may have a functional advantage over unmodified NK cells in the presence of TGF-β-rich MB, warranting further investigation on its potential applications for patients with medulloblastoma.
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