Uncategorized Friday, 2025/03/14
Meng Guangxun's team from the Chinese Academy of Sciences Shanghai Institute of Immunology and Infection cooperated with Liu Chenying's team from the Xinhua Hospital affiliated to the School of Medicine of Shanghai Jiaotong University, and published a research paper entitled “Short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth” in the journal Nature Immunology.
This study found that short IL-18 produced by caspase-3 cleavage exerts inhibitory effects on tumor growth by mobilizing NK cells.
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In this new study, the research team found that cysteine protease-3 (caspase-3) cleaves IL-18 in cancer cells to produce a 15 kDa form of IL-18, which the team refers to as Short IL-18.
Unlike mature IL-18, short IL-18 is not secreted into the extracellular space and does not bind to IL-18 receptor alpha (IL-18R alpha); On the contrary, it enters the nucleus and promotes the phosphorylation of STAT1 at the serine 727 site (Ser727) through cyclin dependent kinase 8 (CDK8), enhancing the expression and secretion of ISG15.
This signaling cascade in cancer cells can mobilize natural killer (NK) cells, enhance their cytotoxic effects, and eliminate various syngeneic tumors and colitis related colorectal cancer in mice. In addition, the research team also found that if the nuclei of colorectal cancer patients are rich in short IL-18, their prognosis is better.
Overall, this study highlights a unique anti-tumor pathway driven by short IL-18, where caspase-3 cleavage produces short IL-18, which mobilizes natural killer (NK) cells, enhances their cytotoxic effects, and inhibits tumor growth.
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Reference
Shen, J., Zhang, Y., Tang, W., Yang, M., Cheng, T., Chen, Y., Yu, S., Guo, Q., Cao, L., Wang, X., Xiao, H., Wang, L., Wang, C., Liu, C., & Meng, G. (2025). Short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth. Nature Immunology, 26(3), 416-428. https://doi.org/10.1038/s41590-024-02074-7