Faculty, Staff and Student Publications
Publication Date
8-12-2024
Journal
Cancer Cell
DOI
10.1016/j.ccell.2024.07.007
PMID
39137729
PMCID
PMC11370652
PubMedCentral® Posted Date
8-12-2025
PubMedCentral® Full Text Version
Author MSS
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.
Keywords
Killer Cells, Natural, Glioblastoma, Interleukins, Humans, Animals, Mice, CCAAT-Enhancer-Binding Protein-delta, Brain Neoplasms, Cell Line, Tumor, Interleukin-15, Xenograft Model Antitumor Assays, Interleukin-21, GBM, NK cells, IL-21, CEBPD
Published Open-Access
yes
Recommended Citation
Shanley, Mayra; Daher, May; Dou, Jinzhuang; et al., "Interleukin-21 Engineering Enhances NK Cell Activity Against Glioblastoma via CEBPD" (2024). Faculty, Staff and Student Publications. 4533.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4533
Graphical Abstract
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