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Peer-reviewedCC BY 4.0Frontiers in Immunology

IL18BP in cancer: a double-edged sword and emerging therapeutic opportunity

  • Chenshen Huang1
  • Yiqing Jiang1
  • Ning Wang2
  • Bing Du3
  • Qi Huang4
4 affiliations
  1. 1Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University
  2. 2Huzhou Central Hospital, The Fifth School of Clinical Medicine of Zhejiang Chinese Medical University
  3. 3Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University
  4. 4Shanghai Tongji Hospital, School of Medicine, Tongji University
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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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Cite

BibTeXRIS
BibTeX
@article{huang2026il18bp,
  title = {{IL18BP in cancer: a double-edged sword and emerging therapeutic opportunity}},
  author = {Chenshen Huang and Yiqing Jiang and Ning Wang and Bing Du and Qi Huang},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1922089},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1922089/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - IL18BP in cancer: a double-edged sword and emerging therapeutic opportunity
AU  - Chenshen Huang
AU  - Yiqing Jiang
AU  - Ning Wang
AU  - Bing Du
AU  - Qi Huang
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1922089
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1922089/full
AB  - 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.
SN  - 1664-3224
ER  -