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Pyroptosis, a newly discovered form of programmed cell death, has shown great potential for enhancing the antitumor immunity of natural killer cells. Consequently, targeting pyroptosis has become an attractive strategy for boosting natural killer cell activity against cancer. In this study, various assays were conducted, including natural killer cell cytotoxicity assays, flow cytometry, xenograft tumor models, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay, to assess natural killer cell\u2013mediated cell killing, as well as gene and protein expressions. The results indicated that euphohelioscopin A, a potential pyroptosis activator, enhances natural killer cell\u2013mediated lysis of tumor cells, resulting in inhibiting tumor growth that could be reversed by natural killer cell depletion. Furthermore, we found that euphohelioscopin A significantly enhanced IFN\u03b3 production in natural killer cells and synergistically upregulated GSDME with IFN\u03b3 in cancer cells. Euphohelioscopin A also increased the cleavage of GSDME, promoting granzyme B\u2013induced pyroptosis, which could be reversed by GSDME knockdown and IFN\u03b3 blockade. Overall, the findings suggested that euphohelioscopin A enhanced natural killer cell\u2013mediated killing of cancer cells by triggering pyroptosis, making euphohelioscopin A a promising pyroptosis activator with great potential for use in natural killer cell\u2013based cancer immunotherapy.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae055","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T14:57:55Z","timestamp":1709909875000},"page":"621-631","source":"Crossref","is-referenced-by-count":6,"title":["Euphohelioscopin A enhances NK cell antitumor immunity through GSDME-triggered pyroptosis"],"prefix":"10.1093","volume":"116","author":[{"given":"Chenyuan","family":"Gong","sequence":"first","affiliation":[{"name":"Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine , 1200 Cai Lun Rd, Pudong New Area, Shanghai 201203 , China"},{"name":"Department of Immunology and 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