ArticleJournal of immunology (Baltimore, Md. : 1950)2014
NK cells with KIR2DS2 immunogenotype have a functional activation advantage to efficiently kill glioblastoma and prolong animal survival.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 57 citations in OpenAlex.
- Heat up and Destroy: Immunotherapy of "Cold" Tumors Using the Example of Glioblastoma.International journal of molecular sciences · 2026Review
- Natural killer cell dysfunction in glioma: from immune evasion to immunotherapy.Frontiers in immunology · 2026Review
- Review
- C/EBPβ-dependent autophagy inhibition hinders NK cell function in cancer.Nature communications · 2024Article
- The nuclear export protein XPO1 provides a peptide ligand for natural killer cells.Science advances · 2024Article
- KIR2DS2+ NK cells in cancer patients demonstrate high activation in response to tumour-targeting antibodies.Frontiers in oncology · 2024Article
- Targeting KIR as a novel approach to improve CAR-NK cell function.Journal of translational genetics and genomics · 2023Article
- Article
- Addressing Natural Killer Cell Dysfunction and Plasticity in Cell-Based Cancer Therapeutics.Cancers · 2023Review
- Advances in NK cell therapy for brain tumors.NPJ precision oncology · 2023Review
- Microarray Profiling of Differentially Expressed Genes in Coronary Artery Bypass Grafts of High-Risk Patients with Postoperative Cognitive Dysfunctions.International journal of environmental research and public health · 2023Article
- Chemo-immune cell therapy by intratumoral injection of adoptive NK cells with capecitabine in gastric cancer xenograft model.BioImpacts : BI · 2023Article
- Natural killer cells in sepsis: Friends or foes?Frontiers in immunology · 2023Review
- The multifaceted mechanisms of malignant glioblastoma progression and clinical implications.Cancer metastasis reviews · 2022Review
- KIR2DS2 Expression Identifies NK Cells With Enhanced Anticancer Activity.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Natural killer cells and immune-checkpoint inhibitor therapy: Current knowledge and new challenges.Molecular therapy oncolytics · 2022Review
- Feeder-Cell-Free and Serum-Free Expansion of Natural Killer Cells Using Cloudz Microspheres, G-Rex6M, and Human Platelet Lysate.Frontiers in immunology · 2022Article
- Cell-Based Therapy for the Treatment of Glioblastoma: An Update from Preclinical to Clinical Studies.Cells · 2021Review
- Review
- Peptide: MHC-based DNA vaccination strategy to activate natural killer cells by targeting killer cell immunoglobulin-like receptors.Journal for immunotherapy of cancer · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastomas (GBMs) are lethal brain cancers that are resistant to current therapies. We investigated the cytotoxicity of human allogeneic NK cells against patient-derived GBM in vitro and in vivo, as well as mechanisms mediating their efficacy. We demonstrate that KIR2DS2 immunogenotype NK cells were more potent killers, notwithstanding the absence of inhibitory killer Ig-like receptor (KIR)-HLA ligand mismatch. FACS-sorted and enriched KIR2DS2(+) NK cell subpopulations retained significantly high levels of CD69 and CD16 when in contact with GBM cells at a 1:1 ratio and highly expressed CD107a and secreted more soluble CD137 and granzyme A. In contrast, KIR2DS2(-) immunogenotype donor NK cells were less cytotoxic against GBM and K562, and, similar to FACS-sorted or gated KIR2DS2(-) NK cells, significantly diminished CD16, CD107a, granzyme A, and CD69 when in contact with GBM cells. Furthermore, NK cell-mediated GBM killing in vitro depended upon the expression of ligands for the activating receptor NKG2D and was partially abrogated by Ab blockade. Treatment of GBM xenografts in NOD/SCID mice with NK cells from a KIR2DS2(+) donor lacking inhibitory KIR-HLA ligand mismatch significantly prolonged the median survival to 163 d compared with vehicle controls (log-rank test, p = 0.0001), in contrast to 117.5 d (log-rank test, p = 0.0005) for NK cells with several inhibitory KIR-HLA ligand mismatches but lacking KIR2DS2 genotype. Significantly more CD56(+)CD16(+) NK cells from a KIR2DS2(+) donor survived in nontumor-bearing brains 3 wk after infusion compared with KIR2DS2(-) NK cells, independent of their proliferative capacity. In conclusion, KIR2DS2 identifies potent alloreactive NK cells against GBM that are mediated by commensurate, but dominant, activating signals.
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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.