دورية أكاديمية
Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD.
| العنوان: | Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD. |
|---|---|
| المؤلفون: | Shanley M; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Daher M; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Dou J; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Li S; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Basar R; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Rafei H; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Dede M; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Gumin J; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Pantaleόn Garcίa J; Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Nunez Cortes AK; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., He S; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Jones CM; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Acharya S; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Fowlkes NW; Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Xiong D; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Singh S; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Shaim H; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Hicks SC; Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Liu B; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Jain A; Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Zaman MF; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Miao Q; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Li Y; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Uprety N; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Liu E; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Muniz-Feliciano L; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Deyter GM; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Mohanty V; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Zhang P; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Evans SE; Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Shpall EJ; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Lang FF; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Chen K; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA., Rezvani K; Department 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. |
| المصدر: | Cancer cell [Cancer Cell] 2024 Aug 12; Vol. 42 (8), pp. 1450-1466.e11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
| مواضيع طبية MeSH: | Killer Cells, Natural*/immunology , Killer Cells, Natural*/metabolism , Glioblastoma*/immunology , Glioblastoma*/genetics , Glioblastoma*/pathology , Glioblastoma*/therapy , Interleukins*/genetics , Interleukins*/metabolism , Interleukins*/immunology , CCAAT-Enhancer-Binding Protein-delta*/metabolism , CCAAT-Enhancer-Binding Protein-delta*/genetics , Brain Neoplasms*/immunology , Brain Neoplasms*/genetics , Brain Neoplasms*/pathology , Brain Neoplasms*/therapy, Humans ; Animals ; Mice ; Cell Line, Tumor ; Interleukin-15/genetics ; Interleukin-15/metabolism ; Interleukin-15/immunology ; Xenograft Model Antitumor Assays |
| مستخلص: | 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. Competing Interests: Declaration of interests M.S., M. Daher, R.B., H.R., S.A., Y.L., N.U., E.L., E.J.S., K.R., and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Takeda Pharmaceutical. R.B., E.J.S., K.R., and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Affimed GmbH. K.R. participates on the Scientific Advisory Board for Avenge Bio, Virogin Biotech, Navan Technologies, Caribou Biosciences, Bit Bio Limited, Replay Holdings, oNKo Innate, and The Alliance for Cancer Gene Therapy ACGT. K.R. is the Scientific founder of Syena. E.J.S. has served on the Scientific Advisory Board for Adaptimmune, Axio, Celaid, FibroBiologics, Navan Technologies, New York Blood Center and Novartis. M Daher participates on the Scientific Advisory Board for Cellsbin. M.S., H.S., E.J.S., and K.R. have filed for a patent (20230074303); “Cell immunotherapy for the treatment of cancer.” (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: CEBPD; GBM; IL-21; NK cells |
| المشرفين على المادة: | MKM3CA6LT1 (interleukin-21) 0 (Interleukins) 142662-43-9 (CCAAT-Enhancer-Binding Protein-delta) 0 (Interleukin-15) |
| تواريخ الأحداث: | Date Created: 20240813 Date Completed: 20240813 Latest Revision: 20240813 |
| رمز التحديث: | 20240814 |
| DOI: | 10.1016/j.ccell.2024.07.007 |
| PMID: | 39137729 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-3686 |
|---|---|
| DOI: | 10.1016/j.ccell.2024.07.007 |