ArticleCancer cell2024
Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD.
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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 69 papers.
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69citing papers in PubMed
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Who cites it
69 citing papers in PubMed.
- Next-generation natural killer cell therapy: bench to bedside and beyond.Signal transduction and targeted therapy · 2026Review
- Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases.MedComm · 2026Review
- IL-15 boosts mesothelin- and CD70-CAR NK cell potency in PDAC without added benefit from dual targeting.Molecular therapy. Oncology · 2026Article
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- Immunotherapy for Glioma: A compartmental framework for resistance and rational combination design.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- 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
- A Microbial Lipid-ATP Synthase Axis Fuels NK Cell Antitumor Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CAR-engineering of innate and innate-like immune cells: a new horizon in adoptive cell therapy for solid tumors.Journal for immunotherapy of cancer · 2026Review
- Therapy-induced remodeling of the tumor immune microenvironment: Mechanistic insights and implications for immunotherapy.Chinese medical journal · 2026Review
- Article
- Constitutive RLI Armoring Enhances CAR-NK Cell Effector Functions but Causes Lethal Toxicity In Vivo.International journal of molecular sciences · 2026Article
- Rapid CAR screening and circRNA-driven CAR-NK cells for persistent shed-resistant immunotherapy.Signal transduction and targeted therapy · 2026Article
- Developing a multimodal therapy for glioblastoma using oncolytic virus delivering CD19 and EGFRvIII antigens and bi-specific CARs.Nature communications · 2026Article
- IL-18 metabolically reprograms CAR-expressing natural killer T cells and enhances their antitumor activity.Molecular therapy : the journal of the American Society of Gene Therapy · 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
- Enhancing cancer killing and natural killer cell persistence by targeting NOXA, a predictor of poor patient survival.Molecular therapy. Oncology · 2026Article
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Review
- CCAAT/enhancer-binding protein delta regulates miRs-4257 and 3156 to attenuate the interleukin 12 through small extracellular vesicle transmission in glioblastoma.Cancer cell international · 2026Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
34 authors.
Mayra ShanleyDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
May DaherDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Jinzhuang DouDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Sufang LiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Rafet BasarDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Hind RafeiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Merve DedeDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Joy GuminDepartment of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Jezreel Pantaleόn GarcίaDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Ana Karen Nunez CortesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Shan HeDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Corry M JonesDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Sunil AcharyaDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Natalie W FowlkesDepartment of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Donghai XiongDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Sanjay SinghDepartment of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Hila ShaimDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Samantha Claire HicksDepartment of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Bin LiuDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Abhinav JainDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Mohammad Fayyad ZamanDepartment of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Qi MiaoDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Ye LiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Nadima UpretyDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Enli LiuDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Luis Muniz-FelicianoDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Gary M DeyterDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Vakul MohantyDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Patrick ZhangDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Scott E EvansDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Elizabeth J ShpallDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Frederick F LangDepartment of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Ken ChenDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Katayoun RezvaniDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA. Electronic address: krezvani@mdanderson.org.
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 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
$41.2MInducible epithelial resistance: a program investigating mechanisms to protect against acute and chronic complications of pneumoniaR35HL144805 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI EVANS, SCOTT E. · 2019 to 2025
$6.2MInformatics for Functional Integration of Heterogeneous Cancer Genome and Transcriptome Sequencing DataU01CA247760 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, KEN · 2020 to 2022
$1.2MNovaSeq6000S10OD024977 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HUFF, VICKI · 2018 to 2018
$995kVeterinary Student Research TrainingT35OD010991 · OD · TEXAS A&M AGRILIFE RESEARCH · PI GADDY, DANA · 2012 to 2025
$920kNCI NIH HHS P30 CA016672NCI NIH HHS P50 CA127001NCI NIH HHS U01 CA247760NHLBI NIH HHS R35 HL144805NIH HHS S10 OD024977NIH HHS T35 OD010991
Abstract
Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune cells with strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM activity of NK cells engineered to express interleukin (IL)-15 or IL-21. Using multiple in vivo models, IL-21 NK cells were superior to IL-15 NK cells both in terms of safety and long-term anti-tumor activity, with locoregionally administered IL-15 NK cells proving toxic and ineffective at tumor control. IL-21 NK cells displayed a unique chromatin accessibility signature, with CCAAT/enhancer-binding proteins (C/EBP), especially CEBPD, serving as key transcription factors regulating their enhanced function. Deletion of CEBPD resulted in loss of IL-21 NK cell potency while its overexpression increased NK cell long-term cytotoxicity and metabolic fitness. These results suggest that IL-21, through C/EBP transcription factors, drives epigenetic reprogramming of NK cells, enhancing their anti-tumor efficacy against GBM.
Indexed as
Brain NeoplasmsCCAAT-Enhancer-Binding Protein-deltaGlioblastomaInterleukinsKiller Cells, NaturalAnimalsCell Line, TumorHumansInterleukin-15Interleukin-21MiceXenograft Model Antitumor AssaysCCAAT-Enhancer-Binding Protein-deltaInterleukin-15Interleukin-21InterleukinsCEBPDGBMIL-21NK cells
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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.