ArticleJournal of translational medicine2011
Time-dependent cytotoxic drugs selectively cooperate with IL-18 for cancer chemo-immunotherapy.
Article in Journal of translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis.Gynecologic oncology · 2012Pooled it
- Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Natural Killer Cell-Derived Extracellular Vesicles Exhibit Cytotoxicity Against Bulk Tumor Cells and Cancer Stem Cells in Triple-Negative Breast Cancer.Nanomaterials (Basel, Switzerland) · 2026Article
- Nanobody-engineered bispecific IL-18 mimetics drive antitumor immunity by engaging CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- It's high-time to re-evaluate the value of induced-chemotherapy for reinforcing immunotherapy in colorectal cancer.Frontiers in immunology · 2023Review
- The immune modifying effects of chemotherapy and advances in chemo-immunotherapy.Pharmacology & therapeutics · 2022Review
- A Phase 2 Clinical Trial of Combination Nivolumab, Ipilimumab, and Paclitaxel in Patients With Untreated Metastatic NSCLC: The OPTIMAL Trial.JTO clinical and research reports · 2022Article
- Neoadjuvant treatment in ovarian cancer: New perspectives, new challenges.Frontiers in oncology · 2022Review
- Chemotherapy reinforces anti-tumor immune response and enhances clinical efficacy of immune checkpoint inhibitors.Frontiers in oncology · 2022Review
- Translational Learnings in the Development of Chemo-Immunotherapy Combination to Bypass the Cold Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma.Frontiers in oncology · 2022Review
- Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors.Nature reviews. Clinical oncology · 2020Review
- MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy.Cancers · 2020Review
- Inhibition of transcription by dactinomycin reveals a new characteristic of immunogenic cell stress.EMBO molecular medicine · 2020Article
- IL-23 and PSMA-targeted duo-CAR T cells in Prostate Cancer Eradication in a preclinical model.Journal of translational medicine · 2020Article
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- Article
- Deficiency of IL-18 Aggravates Esophageal Carcinoma Through Inhibiting IFN-γ Production by CD8Inflammation · 2018Article
- Interleukin-18 has an Important Role in Differentiation and Maturation of Mucosal Mast Cells.Journal of mucosal immunology research · 2018Article
- Role of interleukin-18 in the pathophysiology of allergic diseases.Cytokine & growth factor reviews · 2016Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundTime-dependent chemotherapeutic agents can selectively target tumor cells in susceptible phases of the cell cycle however a fraction of tumor cells in non-vulnerable cell cycle phases remain drug-resistant. Immunotherapy represents a promising approach to overcome the limitation of phase-specific drugs and improve their clinical efficacy. Here, we investigated the potential use of anticancer chemotherapeutic drugs in combination with IL-18, a cytokine with strong immunostimulatory properties.
methodsFour chemotherapeutic drugs commonly used in ovarian cancer were first tested for the ability to increase the immunogenicity and killing of the murine ovarian cancer cell line ID8 in vitro. Chemotherapeutric agents with measured time-dependent immune-enhancing effects were then tested for antitumor effectiveness in vivo in combination with IL-18 immunotherapy using the ID8-Vegf ovarian cancer model.
resultsPaclitaxel or topotecan exposure alone mediated incomplete, time-dependent killing against the murine ovarian cancer cell line ID8 in vitro, whereas carboplatin or gemcitabine mediated comprehensive, dose-dependent killing. In the plateau phase of the time-dependent killing by topotecan or paclitaxel, drug-resistant ID8 cells were more immunogenic with elevated expression of MHC-I and Fas, and increased sensitivity to CTL and Fas agonistic antibody in vitro. Moreover, the antitumor effectiveness of time-dependent agents in vivo was significantly improved with the addition of IL-18 through a T cell-dependent mechanism, while the effectiveness of drugs without significant phase specificity were not.
conclusionsTumor immunotherapy with IL-18 can significantly augment the killing fraction of phase-specific chemotherapeutic drugs and provide survival benefit. The safety profile of IL-18 and its positive interactions with select anticancer chemotherapeutic agents strongly supports the clinical investigation of this combinatorial approach.
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