ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
FLT3L Release by Natural Killer Cells Enhances Response to Radioimmunotherapy in Preclinical Models of HNSCC.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- NK cell-mediated tumor cell killing by bispecific innate cell engagers induces ADCC-mediated activation of primary human dendritic cells.Oncoimmunology · 2026Article
- Radiotherapy and immunotherapy in cancer treatment: mechanisms of clinical synergy.The Journal of clinical investigation · 2026Review
- Identification of the Dynamic Expression Patterns of Immune Genes in the Peripheral Blood of Acute Ischemic Stroke Patients.Biochemical genetics · 2026Article
- The effect of neoadjuvant radiotherapy on immune cell infiltrates in myxofibrosarcoma.Immuno-oncology technology · 2026Article
- Unraveling the molecular landscape: an overview on gene expression, epigenetic alterations, and therapeutic challenges in head and neck squamous cell carcinoma.Molecular genetics and genomics : MGG · 2026Review
- IL2/IL15 Signaling Induces NK Cell Production of FLT3LG, Augmenting Anti-PD-1 Immunotherapy.Cancer immunology research · 2026Article
- Radiation-Induced Immune Responses from the Tumor Microenvironment to Systemic Immunity.Cancers · 2025Review
- Engineered oncolytic virus OH2-FLT3L enhances antitumor immunity via dendritic cell activation.Molecular therapy. Oncology · 2025Article
- Article
- Innate immune cells in tumor microenvironment: A new frontier in cancer immunotherapy.iScience · 2024Review
- Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC.bioRxiv : the preprint server for biology · 2024Article
- High FLT3 expression increases immune-cell infiltration in the tumor microenvironment and correlates with prolonged disease-free survival in patients with non-small cell lung cancer.Molecular oncology · 2024Article
- IL7 in combination with radiotherapy stimulates a memory T-cell response to improve outcomes in HNSCC models.Cancer immunology, immunotherapy : CII · 2024Article
- An investigator-initiated clinical study in patients with refractory or recurrent solid tumors: 'R-ISV-FOLactis' trial.Future oncology (London, England) · 2024Article
- BCG immunotherapy promotes tumor-derived T-cell activation through the FLT3/FLT3LG pathway in bladder cancer.Journal of Cancer · 2024Article
- Altered extracellular matrix correlates with an immunosuppressive tumor microenvironment and disease progression in younger adults with oral cavity squamous cell carcinoma.Frontiers in oncology · 2024Article
- A comprehensive prognostic score for head and neck squamous cancer driver genes and phenotype traits.Discover oncology · 2023Article
- Selective targeting of IL2Rβγ combined with radiotherapy triggers CD8- and NK-mediated immunity, abrogating metastasis in HNSCC.Cell reports. Medicine · 2023Article
- Targeting oral tumor microenvironment for effective therapy.Cancer cell international · 2023Review
- Radiation-induced tumor immune microenvironments and potential targets for combination therapy.Signal transduction and targeted therapy · 2023Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
purposeNatural killer (NK) cells are type I innate lymphoid cells that are known for their role in killing virally infected cells or cancer cells through direct cytotoxicity. In addition to direct tumor cell killing, NK cells are known to play fundamental roles in the tumor microenvironment through secretion of key cytokines, such as FMS-like tyrosine kinase 3 ligand (FLT3L). Although radiotherapy is the mainstay treatment in most cancers, the role of radiotherapy on NK cells is not well characterized. EXPERIMENTAL
designThis study combines radiation, immunotherapies, genetic mouse models, and antibody depletion experiments to identify the role of NK cells in overcoming resistance to radiotherapy in orthotopic models of head and neck squamous cell carcinoma.
resultsWe have found that NK cells are a crucial component in the development of an antitumor response, as depleting them removes efficacy of the previously successful combination treatment of radiotherapy, anti-CD25, and anti-CD137. However, in the absence of NK cells, the effect can be rescued through treatment with FLT3L. But neither radiotherapy with FLT3L therapy alone nor radiotherapy with anti-NKG2A yields any meaningful tumor growth delay. We also identify a role for IL2 in activating NK cells to secrete FLT3L. This activity, we show, is mediated through CD122, the intermediate affinity IL2 receptor, and can be targeted with anti-CD25 therapy.
conclusionsThese findings highlight the complexity of using radio-immunotherapies to activate NK cells within the tumor microenvironment, and the importance of NK cells in activating dendritic cells for increased tumor surveillance.
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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.