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Interleukin-18 armours antitumour immune effectors
Akshat Sharma1, Gina G Bishara2, Scott H Olejniczak2
1Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Nature Reviews. Immunology
|July 16, 2026
Summary
Interleukin-18 (IL-18) shows therapeutic potential in cancer immunity by enhancing T cell responses and natural killer cell activity. Understanding IL-18
Area of Science:
- Immunology
- Oncology
- Cytokine Biology
Background:
- Interleukin-18 (IL-18) is a key cytokine in innate and adaptive immunity, particularly in anti-tumor and anti-viral responses.
- Therapeutic strategies are emerging to leverage IL-18 for cancer treatment, including engineered cell therapies.
- Translational challenges include understanding molecular mechanisms of IL-18 action and resistance in the tumor microenvironment.
Purpose of the Study:
- To review the fundamental biology of IL-18, including its regulation by IL-18BP and IL-37.
- To discuss IL-18's role in promoting anti-tumor immunity via IFNγ production, M1 macrophage polarization, and T cell responses.
- To highlight preclinical and emerging therapeutic strategies involving IL-18 and review early clinical findings.
Main Methods:
- Literature review of IL-18 biology, regulatory networks, and therapeutic applications.
- Analysis of IL-18's role in modulating the tumor microenvironment and immune cell functions.
- Synthesis of preclinical models and early clinical study results for IL-18-based therapies.
Main Results:
- IL-18 promotes IFNγ production, M1 macrophage polarization, CD8+ T cell, Th1 cell, and NK cell responses, contributing to durable T cell memory.
- Preclinical models demonstrate efficacy of IL-18 delivery via dendritic cells and cellular therapies.
- Emerging strategies include IL-18BP blockade and IL-18-secreting CAR T cells.
Conclusions:
- IL-18 holds significant promise for enhancing cancer immunotherapy by modulating the tumor microenvironment.
- Further research is needed to address the dual pro-tumor and anti-tumor roles of IL-18 and optimize clinical translation.
- Understanding IL-18's complex mechanisms is crucial for guiding clinical trial design and patient selection.
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