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Genetically modified NK\u201092MI\u00a0cells, which can release IL\u20102 to sustain their viability, have been identified as a promising alternative. This adaptation addresses the negative consequences of systemic IL\u20102 administration. The role of PSD\u201095\/discs large\/ZO\u20101 (PDZ)\u2010binding kinase (PBK) in cancer development is recognized, but its effects on immunity are not fully understood. This study explores how PBK expression influences the ability of NK\u201092MI cells to infiltrate ovarian tumours. Elevated levels of PBK expression have been found in various cancers, including ovarian cancer (OV), with analyses showing higher PBK mRNA levels in tumour tissues compared to normal ones. Immunohistochemistry has confirmed increased PBK expression in OV tissues. Investigations into PBK's role in immune regulation reveal its association with immune cell infiltration, indicating a potentially compromised immune environment in OV with high PBK expression. The small\u2010molecule inhibitor HI\u2010TOPK\u2010032, which inhibits PBK, enhances the cytotoxicity of NK\u201092MI cells toward OV cells. It increases the production of interferon\u2010\u03b3 and tumour necrosis factor\u2010\u03b1, reduces apoptosis and encourages cell proliferation. Mechanistic studies showed that contact with OV cells treated with HI\u2010TOPK\u2010032 upregulates CD107a on NK\u201092 cells. In vivo studies demonstrated that HI\u2010TOPK\u2010032 improves the antitumour effects of NK\u201092MI cells in OVCAR3<jats:sup>Luc<\/jats:sup> xenografts, extending survival without significant side effects. Safety assessments in mice confirm HI\u2010TOPK\u2010032's favourable safety profile, highlighting its potential as a viable antitumour therapy. These results suggest that combining NK\u201092MI cells with HI\u2010TOPK\u2010032 enhances antitumour effectiveness against OV, indicating a promising, safe and effective treatment strategy that warrants further clinical investigation.<\/jats:p>","DOI":"10.1111\/bcpt.14002","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T11:29:55Z","timestamp":1710847795000},"page":"629-642","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Small\u2010molecule inhibitor HI\u2010TOPK\u2010032 improves NK\u201092MI cell infiltration into ovarian tumours"],"prefix":"10.1111","volume":"134","author":[{"given":"Mengqi","family":"Deng","sequence":"first","affiliation":[{"name":"Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing Maternal and Child Health Care Hospital  Beijing 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