ArticlePloS one2011
IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Immunotherapy as a Promising Treatment for Prostate Cancer: A Systematic Review.Journal of immunology research · 2017Pooled it
- Periprostatic adipose tissue-derived adipokine profile in prostate cancer patients reveals two distinct molecular phenotypes linked to obesity-related comorbidities: multifaceted role of lipocalin-2.Cell communication and signaling : CCS · 2026Article
- IL-18-armed oncolytic vaccinia virus remodels the suppressive microenvironment via macrophage and Treg modulation in lymphoma.Cancer immunology, immunotherapy : CII · 2026Article
- Caerin 1.1/1.9 interfere KHDRBS1-DDX5 regulatory axis to induce IL-18 mediated pyroptosis in a HeLa cell tumour model.Scientific reports · 2025Article
- Unleashing the power of peptides in prostate cancer immunotherapy: mechanism, facts and perspectives.Frontiers in pharmacology · 2025Review
- Osteoarthritis as a Systemic Disease Promoted Prostate Cancer In Vivo and In Vitro.International journal of molecular sciences · 2024Article
- The investigation of oncolytic viruses in the field of cancer therapy.Frontiers in oncology · 2024Review
- Exploring the role of the inflammasomes on prostate cancer: Interplay with obesity.Reviews in endocrine & metabolic disorders · 2023Review
- A Recombinant Oncolytic Pseudorabies Virus ExpressingMicroorganisms · 2023Article
- Preclinical and Clinical Research Models of Prostate Cancer: A Brief Overview.Life (Basel, Switzerland) · 2022Review
- Histone deacetylase 6-mediated downregulation of TMEM100 expedites the development and progression of non-small cell lung cancer.Human cell · 2022Article
- ATR Inhibition Induces CDK1-SPOP Signaling and Enhances Anti-PD-L1 Cytotoxicity in Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Reengineering Tumor Microenvironment with Sequential Interleukin Delivery.Bioengineering (Basel, Switzerland) · 2021Article
- Human bone marrow-derived stromal cell behavior when injected directly into the bone marrow of NOD-scid-gamma mice pre-conditioned with sub-lethal irradiation.Stem cell research & therapy · 2021Article
- Cardiac, Hepatic and Renal Dysfunction and IL-18 Polymorphism in Breast, Colorectal, and Prostate Cancer Patients.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer.Cancers · 2020Article
- Effect of lentiviral vector-packaged interleukin-18 gene on the malignant behavior of lung cancer.Experimental and therapeutic medicine · 2020Article
- Protein modeling, molecular network and molecular dynamics study of newly sequenced interleukin-18 (IL-18) gene in Mus musculus.Journal of cellular physiology · 2019Article
- The Effects of Matrine in Combination with Docetaxel on Castration-Resistant (Androgen-Independent) Prostate Cancer.Cancer management and research · 2019Article
- Inflammation and NF-κB Signaling in Prostate Cancer: Mechanisms and Clinical Implications.Cells · 2018Review
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4(+) and CD8(+) T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1(-/-) mice or in mice depleted of CD4(+) and/or CD8(+) cells than in normal mice. The tumors in RAG1(-/-) mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.
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Registered trials
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