ArticleGynecologic oncology2019
Cytokine-induced memory-like natural killer cells have enhanced function, proliferation, and in vivo expansion against ovarian cancer cells.
Article in Gynecologic oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 115 citations in OpenAlex.
- Tumor microenvironment-driven natural killer cell diversity: mechanisms and therapeutic opportunities.Cancer biology & medicine · 2026Review
- Metabolic licensing and restriction of innate immunity in the tumor microenvironment.Frontiers in immunology · 2026Review
- Natural Killer Cell Therapy in Ovarian Cancer: From Preclinical Potentials to Clinical Applications and Combination Strategies.International journal of biological sciences · 2026Review
- Phenotypic, proteomic, and functional analyses of cytokine-induced memory-like NK cells show two distinct subsets based on CD16 expression.Scientific reports · 2025Article
- Cytokine-induced memory-like natural killer cells in systemic lupus erythematosus patients.Advances in rheumatology (London, England) · 2025Article
- Novel tetrameric bispecific KK-LC-1×CD16A-armed memory-like NK cells enhance antitumor efficacy in gastric cancer.Journal for immunotherapy of cancer · 2025Article
- Prospects and limitations of NK cell adoptive therapy in clinical applications.Cancer metastasis reviews · 2025Review
- Elephant in the room: natural killer cells don't forget HIV either.Current opinion in HIV and AIDS · 2025Review
- CD56Journal for immunotherapy of cancer · 2025Article
- Natural killer cell exhaustion in ovarian cancer: from molecular suppression to therapeutic revival.Frontiers in immunology · 2025Review
- Tertiary lymphoid structures: exploring opportunities to improve immunotherapy in ovarian cancer.Frontiers in immunology · 2025Review
- Primordial Cells Bridging the Gap Between Innate and Adaptive Immunity.Advances in experimental medicine and biology · 2025Review
- Natural killer cell memory: challenges and opportunities for cancer immunotherapy.Cancer biology & therapy · 2024Review
- Role of Non-Binding T63 Alteration in IL-18 Binding.International journal of molecular sciences · 2024Article
- Oncolytic virotherapy augments self-maintaining natural killer cell line cytotoxicity against neuroblastoma.Cancer immunology, immunotherapy : CII · 2024Article
- CAR memory-like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer.Science advances · 2024Article
- Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Review
- NK cells as powerful therapeutic tool in cancer immunotherapy.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy.Cells · 2024Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveNatural killer (NK) cells are lymphocytes well suited for adoptive immunotherapy. Attempts with adoptive NK cell immunotherapy against ovarian cancer have proven unsuccessful, with the main limitations including failure to expand and diminished effector function. We investigated if incubation of NK cells with interleukin (IL)-12, IL-15, and IL-18 for 16h could produce cytokine-induced memory-like (CIML) NK cells capable of enhanced function against ovarian cancer.
methodsNK cells were preactivated briefly with IL-12, IL-15, and IL-18, rested, then placed against ovarian cancer targets to assess phenotype and function via flow cytometry. Real-time NK-cell-mediated tumor-killing was evaluated. Using ascites cells and cell-free ascites fluid, NK cell proliferation and function within the immunosuppressive microenvironment was evaluated in vitro. Finally, CIML NK cells were injected intraperitoneal (IP) into an in vivo xenogeneic mouse model of ovarian cancer.
resultsCIML NK cells demonstrate enhanced cytokine (IFN-γ) production and NK-cell-mediated killing of ovarian cancer. NK cells treated overnight with cytokines led to robust activation characterized by temporal shedding of CD16, induction of CD25, and enhanced proliferation. CIML NK cells proliferate more with enhanced effector function compared to controls in an immunosuppressive microenvironment. Finally, human CIML NK cells exhibited potent antitumor effects within a xenogeneic mouse model of ovarian cancer.
conclusionsCIML NK cells have enhanced functionality and persistence against ovarian cancer in vitro and in vivo, even when exposed to ascites fluid. These findings provide a strategy for NK cell-based immunotherapy to circumvent the immunosuppressive nature of ovarian cancer.
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