ArticleCancer immunology research2023
LEF1 Drives a Central Memory Program and Supports Antitumor Activity of Natural Killer T Cells.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Thymic APC Networks Orchestrate T-Cell Selection: Mechanisms and Therapeutic Opportunities in Immune Disorders.Immunology · 2026Review
- 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
- Upregulation of TNFR2 Precedes TOX Expression by Exhausted T cells and Restricts Antitumor and Antiviral Immunity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Conditional T and NK cell antagonism by a giant and highly conserved orthopoxvirus virulence factor.Research square · 2026Article
- Metabolic control of innate-like T cells.Nature reviews. Immunology · 2026Review
- From iPSC to manufactured iNK cells using CombiCult® screening platform.Frontiers in cell and developmental biology · 2026Article
- Facts and Hopes of Chimeric Antigen Receptor-Redirected NK T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues.Cell reports · 2025Article
- PRDM1 Is a Key Regulator of the NKT-cell Central Memory Program and Effector Function.Cancer immunology research · 2025Article
- Decreased expression of LEF1 caused defective decidualization by inhibiting IL-11 expression in patients with adenomyosis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance.Frontiers in immunology · 2025Article
- Regulatory T cell-associated gene signature correlates with prognostic risk and immune infiltration in patients with breast cancer.Translational cancer research · 2024Article
- The relationship between immune cells and prostate cancer, and the mediating role of metabolites: a Mendelian randomization study.Scientific reports · 2024Article
- Human CD4Immunology · 2024Article
- A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells (TCR-T cells) against hepatocellular carcinoma.Signal transduction and targeted therapy · 2024Article
- IL-12 reprograms CAR-expressing natural killer T cells to long-lived Th1-polarized cells with potent antitumor activity.Nature communications · 2024Article
- Reprogramming T cell differentiation and exhaustion in CAR-T cell therapy.Journal of hematology & oncology · 2023Review
- CAR-NKT cell therapy: a new promising paradigm of cancer immunotherapy.Cancer cell international · 2023Review
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16 authors at 1 institution in 1 country.
Funding
Abstract
Vα24-invariant natural killer T cells (NKT) possess innate antitumor properties that can be exploited for cancer immunotherapy. We have shown previously that the CD62L+ central memory-like subset of these cells drives the in vivo antitumor activity of NKTs, but molecular mediators of NKT central memory differentiation remain unknown. Here, we demonstrate that relative to CD62L- cells, CD62L+ NKTs express a higher level of the gene encoding the Wnt/β-catenin transcription factor lymphoid enhancer binding factor 1 (LEF1) and maintain active Wnt/β-catenin signaling. CRISPR/Cas9-mediated LEF1 knockout reduced CD62L+ frequency after antigenic stimulation, whereas Wnt/β-catenin activator Wnt3a ligand increased CD62L+ frequency. LEF1 overexpression promoted NKT expansion and limited exhaustion following serial tumor challenge and was sufficient to induce a central memory-like transcriptional program in NKTs. In mice, NKTs expressing a GD2-specific chimeric-antigen receptor (CAR) with LEF1 demonstrated superior control of neuroblastoma xenograft tumors compared with control CAR-NKTs. These results identify LEF1 as a transcriptional activator of the NKT central memory program and advance development of NKT cell-based immunotherapy. See related Spotlight by Van Kaer, p. 144.
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Registered trials
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.