ArticleThe Journal of clinical investigation2021
Targeting the αv integrin/TGF-β axis improves natural killer cell function against glioblastoma stem cells.
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Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers.
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201citing papers in PubMed
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201 citing papers in PubMed, 239 citations in OpenAlex.
- Next-generation natural killer cell therapy: bench to bedside and beyond.Signal transduction and targeted therapy · 2026Review
- Natural Killer Cell-Derived Extracellular Vesicle Preparations Demonstrate Potent Antitumor Activity Against Human Glioblastoma In Vitro and In Vivo.Journal of extracellular biology · 2026Article
- Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases.MedComm · 2026Review
- Synergistic Regulation of Tumor Immunity by Integrins and Lectins: From Molecular Mechanisms to Dual-Targeted Therapy.International journal of molecular sciences · 2026Review
- LRIG2 suppresses NK cell-induced GSDME-mediated pyroptosis via the LAMP1-STAT3 pathway in glioma.Journal for immunotherapy of cancer · 2026Article
- Immunotherapy for Glioma: A compartmental framework for resistance and rational combination design.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Cellular adhesion-dependent 3D morphogenesis indicating brain tumor aggressiveness and chemosensitivity in spherical cavity culture.Experimental hematology & oncology · 2026Article
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- CAR-NK cell therapy for hematological malignancies.Blood advances · 2026Review
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Circumventing Ewing sarcoma tumor microenvironment resistance by IL1RAP CAR-modified TGFβ1-imprinted natural killer cells in combination with IL-15 agonist and anti-GD2 antibody.Journal for immunotherapy of cancer · 2026Article
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Symbiotic exclusivity between CLOCK and TFPI2 drives stemness and immunosuppression in glioblastoma models.The Journal of clinical investigation · 2026Article
- Rapid CAR screening and circRNA-driven CAR-NK cells for persistent shed-resistant immunotherapy.Signal transduction and targeted therapy · 2026Article
- The TGF-βR1 inhibitor galunisertib re-shapes the PDAC-TME by limiting decidual-like natural killer cells polarization.Cell death & disease · 2026Article
- Glioblastoma-natural killer cell crosstalk: insights from dynamic spheroid models reveal the importance of secreted cytokines and the CD155 axis.Cell communication and signaling : CCS · 2026Article
- Heat up and Destroy: Immunotherapy of "Cold" Tumors Using the Example of Glioblastoma.International journal of molecular sciences · 2026Review
- <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>.Oncology reports · 2026Review
141 more citing papers are in PubMed but not listed here.
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Authors and funding
50 authors at 5 institutions in 5 countries.
Hila ShaimDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Mayra ShanleyDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Rafet BasarDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
May DaherDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Joy GuminDepartment of Neurosurgery.
Daniel B ZamlerDepartment of Genomic Medicine.
Nadima UpretyDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Fang WangDepartment of Bioinformatics and Computational Biology.
Yuefan HuangDepartment of Bioinformatics and Computational Biology.
Konrad GabrusiewiczDepartment of Neurosurgery.
Qi MiaoDepartment of Bioinformatics and Computational Biology.
Jinzhuang DouDepartment of Bioinformatics and Computational Biology.
Abdullah AlsulimanDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Lucila N KerbauyDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sunil AcharyaDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Vakul MohantyDepartment of Bioinformatics and Computational Biology.
Mayela MendtDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sufang LiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
JunJun LuDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jun WeiDepartment of Neurosurgery.
Natalie W FowlkesDepartment of Veterinary Medicine and Surgery.
Elif GokdemirDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Emily L EnsleyDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Mecit KaplanDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cynthia KassabDepartment of Neurosurgery.
Li LiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Gonca OzcanDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Pinaki P BanerjeeDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Yifei ShenDepartment of Bioinformatics and Computational Biology.
April L GilbertDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Corry M JonesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Mustafa BdiwiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ana K Nunez-CortesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Enli LiuDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jun YuDepartment of Neurosurgery.
Nobuhiko ImahashiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Luis Muniz-FelicianoDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ye LiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jian HuDepartment of Cancer Biology, and.
Giulio DraettaDepartment of Genomic Medicine.
David MarinDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Dihua YuDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Stephan MielkeDepartment of Internal Medicine II, University Medical Center Würzburg, Würzburg, Germany.
Matthias EyrichDepartment of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Medical Center Würzburg, Würzburg, Germany.
Richard E ChamplinDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ken ChenDepartment of Bioinformatics and Computational Biology.
Frederick F LangDepartment of Neurosurgery.
Elizabeth J ShpallDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Amy B HeimbergerDepartment of Neurosurgery.
Katayoun RezvaniDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The University of Texas MD Anderson Cancer Center · USCenter for Genomic Science · ITUniversitätsklinikum Würzburg · DEUniversity of Veterinary Medicine · HUUniversity of Würzburg · DE
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MTropism Enhanced Oncolytic Adenovirus for the Treatment of Brain TumorsP50CA127001 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Juan Fueyo · 2008 to 2026
$41.2MModulation of Microglia and T Cell Interactions in Malignant GliomaR01CA120813 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HEIMBERGER, AMY BETH, RAO, GANESH · 2007 to 2025
$4.7MNCI NIH HHS P30 CA016672NCI NIH HHS P50 CA127001NCI NIH HHS R01 CA120813
Abstract
Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed that GBM tumor-infiltrating NK cells acquired an altered phenotype associated with impaired lytic function relative to matched peripheral blood NK cells from patients with GBM or healthy donors. We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via αv integrin-mediated TGF-β activation. Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-β signaling or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the αv integrin/TGF-β axis as a potentially useful therapeutic target in GBM.
Indexed as
AnimalsFemaleGlioblastomaHeterograftsHumansIntegrinsKiller Cells, NaturalMaleMiceNeoplasm ProteinsNeoplasm TransplantationNeoplastic Stem CellsReceptor, Transforming Growth Factor-beta Type IITransforming Growth Factor betaIntegrinsITGA5 protein, humanNeoplasm ProteinsReceptor, Transforming Growth Factor-beta Type IITGFBR2 protein, humanTransforming Growth Factor betaBrain cancerCancer immunotherapyImmunologyNK cells
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