ArticleOncotarget2017
Tumor-derived IL-18 induces PD-1 expression on immunosuppressive NK cells in triple-negative breast cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 87 citations in OpenAlex.
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- NOXA/MCL-1 axis determines cell-death decision between apoptosis and a GSDME-dependent cell death associated with production of inflammatory cytokines upon treatment of breast cancer cells with antimitotics.Cell death & disease · 2026Article
- Programmed cell death-1: from a T-cell immune checkpoint to a regulator of Natural Killer cell biology.Frontiers in cell and developmental biology · 2026Review
- Overcoming NK cell resistance in triple-negative breast cancer via adcc with a humanized anti-CD147 antibody.Cancer immunology, immunotherapy : CII · 2025Article
- Age-related and postmenopausal breast cancer progression and treatment management: The significance of pro-inflammatory cytokines and CXC chemokines.Genes & diseases · 2025Review
- Targeting kinases that regulate programmed cell death: a new therapeutic strategy for breast cancer.Journal of translational medicine · 2025Review
- Inflammasomes in lymphocytes as therapeutic targets.Translational oncology · 2025Article
- Systematic Analysis of an Immune-Related Gene Signature for Predicting Prognosis and Immune Characteristics in Primary Lower Grade Glioma.BioMed research international · 2025Article
- Caspase-1-dependent spatiality in triple-negative breast cancer and response to immunotherapy.Nature communications · 2024Article
- Investigating tumor immunogenicity in breast cancer: deciphering the tumor immune response to enhance therapeutic approaches.Frontiers in immunology · 2024Review
- Fat Biology in Triple-Negative Breast Cancer: Immune Regulation, Fibrosis, and Senescence.Journal of obesity & metabolic syndrome · 2023Review
- IL-18 serves as a main effector of CAF-derived METTL3 against immunosuppression of NSCLC via driving NF-κB pathway.Epigenetics · 2023Article
- A potential immunotherapy target for breast cancer: parenchymal and immune-stromal expression of the NLRP3 inflammasome pathway.BMC cancer · 2023Article
- Bridging Pyroptosis and Immunity: A Comprehensive Study of the Pyroptosis-Related Long Non-Coding RNA Signature in Breast Cancer.Life (Basel, Switzerland) · 2023Article
- Targeting PD-1/PD-L1 in cancer immunotherapy: An effective strategy for treatment of triple-negative breast cancer (TNBC) patients.Genes & diseases · 2023Review
- Functional crosstalk and regulation of natural killer cells in tumor microenvironment: Significance and potential therapeutic strategies.Genes & diseases · 2023Review
- Targeting pyroptosis in breast cancer: biological functions and therapeutic potentials on It.Cell death discovery · 2023Review
- Potentiation of natural killer cells to overcome cancer resistance to NK cell-based therapy and to enhance antibody-based immunotherapy.Frontiers in immunology · 2023Review
- Article
- Immunotherapy and immunoengineering for breast cancer; a comprehensive insight into CAR-T cell therapy advancements, challenges and prospects.Cellular oncology (Dordrecht, Netherlands) · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWhile the inflammatory cytokine interleukin-18 (IL-18) is known to activate natural killer (NK) cells, its precise role in cancer is controversial. In this study, we investigated the role of tumor-derived IL-18 on peripheral blood NK cells in breast cancer patients.
resultsIn breast cancer cell lines, IL-18 was expressed and secreted in the triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and HCC-70 but not in MCF-7 cells. The immature and non-cytotoxic CD56dimCD16dim/- NK cell fraction was increased following co-culture with MDA-MB-231 cells, and this increase was not observed with tumor cells transfected with siRNA for IL-18 or in MCF-7 cells. In addition, tumor-derived IL-18 increased PD-1 expression on CD56dimCD16dim/- NK cells, although no effect on PD-L1 expression in tumor cells was observed. Among EBC patients, serum IL-18 levels were significantly increased in those with a TNBC subtype compared to levels from patients with other subtypes, and the IL-18 levels were strongly associated with poor survival. Similarly, serum IL-18 and CD56dimCD16dim/- NK cells were also increased in patients with metastatic TNBC who had progressive disease following cytotoxic chemotherapy. EXPERIMENTAL
designWe performed in vitro experiments in breast cancer cell lines, measured cytokine levels by RT-qPCR, western blot, and ELISA, and analyzed NK cell subsets by flow cytometry. For clinical validation, we collected and analyzed blood sample from patients with early breast cancer (EBC, N = 545) and metastatic breast cancer (MBC, N = 42).
conclusionsOur data revealed that tumor-derived IL-18 is associated with bad prognosis in patients with TNBC. Tumor-derived IL-18 increased the immunosuppressive CD56dimCD16dim/- NK cell fraction and induced PD-1 expression on these NK cells.
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