ReviewFrontiers in immunology2026
IL18BP in cancer: a double-edged sword and emerging therapeutic opportunity.
Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Interleukin-18-binding protein (IL18BP) is a pivotal extracellular gatekeeper of IL-18 activity and an emerging therapeutic target in cancer. By sequestering mature IL-18, IL18BP controls the receptor-accessible free ligand within the tumor microenvironment. The consequences are highly context dependent: IL18BP may suppress beneficial natural killer- and T-cell responses, yet also restrain IL-18-driven immune tolerance, inflammation, and metastatic adaptation. Here, we outline the mechanisms, cellular sources, tissue distribution, and cancer-specific roles of the IL-18/IL18BP axis. We emphasize that total, bound, and free IL-18 are biologically distinct and must be interpreted alongside IL18BP abundance, receptor competence, responder-cell identity, and treatment context. Accordingly, IL18BP blockade or decoy-resistant IL-18 agonists may restore antitumor immunity in selected settings, whereas preserving or enhancing IL-18 neutralization may be protective in others. Precision therapeutic tuning, rather than indiscriminate blockade, will be essential to translate this axis into effective biomarkers and cancer treatments.
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