ArticleJournal for immunotherapy of cancer2019
Human double negative T cells target lung cancer via ligand-dependent mechanisms that can be enhanced by IL-15.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 80 citations in OpenAlex.
- IFITM1 enhances anti-tumor function of unconventional TCRαβ double negative T cells by upregulating mitophagy.Science China. Life sciences · 2026Article
- FcεRIγ reinforces double-negative T cell-mediated antibody-dependent cellular cytotoxicity against tumor cells.Journal of molecular cell biology · 2026Article
- Article
- A pan-cancer single cell landscape reveals heterogeneity and functional diversity of double-negative T cells.Molecular cancer · 2026Article
- Proliferative double-negative T (DNT)-cell responses to PD-1 blockade therapy were positively correlated with good clinical outcomes in non-small cell lung cancer patients.Pakistan journal of medical sciences · 2026Article
- Exercise Impacts Liver Disease: Balancing Metabolic and Immune Homeostasis.International journal of biological sciences · 2026Review
- Unraveling the molecular-pathological characteristics and cellular complexity of the tumor immune microenvironment in metastatic non-small cell lung cancer.Cell communication and signaling : CCS · 2025Review
- Recent advances in universal chimeric antigen receptor T cell therapy.Journal of hematology & oncology · 2025Review
- Review
- CSTF2-impeded innate αβ T cell infiltration and activation exacerbate immune evasion of pancreatic cancer.Cell death and differentiation · 2025Article
- Causal association of breast cancer with immune cells: new evidence from bi-directional Mendelian randomization using GWAS summary statistics.BMC cancer · 2025Article
- Presetting CAR-T cells during ex vivo biomanufacturing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Characterization and effective expansion of CD4Molecular therapy. Methods & clinical development · 2025Article
- Humanized Mouse Models for Immuno-Oncology Research: A Review and Implications in Lung Cancer Research.JTO clinical and research reports · 2025Review
- Purinergic signaling by TCRαβScience bulletin · 2025Article
- Allogeneic DNT cell therapy synergizes with T cells to promote anti-leukemic activities while suppressing GvHD.Journal of experimental & clinical cancer research : CR · 2025Article
- Double-negative T cells with a distinct transcriptomic profile are abundant in the peripheral blood of patients with breast cancer.Breast cancer research and treatment · 2025Article
- Modulation of double-negative T cells by Huang-Lian-Jie-Du Decoction attenuates neuroinflammation in ischemic stroke: insights from single-cell transcriptomics.Frontiers in immunology · 2025Article
- Flow-cytometry Assessment of DNA content and Immunophenotyping of Immune-cells in Lymph-node-specimens as a Potential Diagnostic Signature of Aggressiveness in B-Non-Hodgkin Lymphomas.Annals of hematology · 2024Article
- Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundThe advents of novel immunotherapies have revolutionized the treatment of cancer. Adoptive cellular therapies using chimeric antigen receptor T (CAR-T) cells have achieved remarkable clinical responses in B cell leukemia and lymphoma but the effect on solid tumors including lung cancer is limited. Here we present data on the therapeutic potential of allogeneic CD3
methodsDNTs were enriched and expanded ex vivo from healthy donors and phenotyped by flow cytometry. Functionally, their cytotoxicity was determined against primary and established non-small-cell lung cancer (NSCLC) cell lines in vitro or through in vivo adoptive transfer into xenograft models. Mechanistic analysis was performed using blocking antibodies against various cell surface and soluble markers. Furthermore, the role of IL-15 on DNT function was determined.
resultsWe demonstrated that ex vivo expanded DNTs can effectively lyse various human NSCLC cells in vitro and inhibit tumor growth in xenograft models. Expanded DNTs have a cytotoxic phenotype, as they express NKp30, NKG2D, DNAM-1, membrane TRAIL (mTRAIL), perforin and granzyme B, and secrete IFNγ and soluble TRAIL (sTRAIL). DNT-mediated cytotoxicity was dependent on a combination of tumor-expressed ligands for NKG2D, DNAM-1, NKp30 and/or receptors for TRAIL, which differ among different NSCLC cell lines. Furthermore, stimulation of DNTs with IL-15 increased expression of effector molecules on DNTs, their TRAIL production and cytotoxicity against NSCLC in vitro and in vivo.
conclusionHealthy donor-derived DNTs can target NSCLC in vitro and in vivo. DNTs recognize tumors via innate receptors which can be up-regulated by IL-15. DNTs have the potential to be used as a novel adoptive cell therapy for lung cancer either alone or in combination with IL-15.
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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.