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Previous studies have identified the transcription factor IRF5 as a characteristic gene of M1\u2010like macrophages, highlighting its crucial role in promoting antitumor immune responses. In this study, we developed an engineered M1\u2010like macrophage exosomes expressing IRF5 (IRF5 M1\u2010exos) and demonstrated their ability to inhibit proliferation, migration, and invasion of lung cancer cells. Moreover, our experiments using a nude mouse model revealed that IRF5 M1\u2010exos exerted potent therapeutic effects by effectively suppressing tumor growth. Notably, the mechanism by which IRF5 exerts its antitumor function through HLA\u2010E regulation in lung cancer has not been fully elucidated. Here, we identified HLA\u2010E as a downstream target gene of IRF5 and demonstrated that the overexpression of HLA\u2010E can counteract the tumor\u2010promoting effects induced by si\u2010IRF5 M1\u2010exos. These results suggest that M1 macrophage\u2010derived exosomes, enriched with the transcription factor IRF5, exhibit potent antitumor activity by up\u2010regulating HLA\u2010E in lung cancer cells. Therefore, IRF5 M1\u2010exos represent an attractive therapeutic strategy for lung cancer.<\/jats:p>","DOI":"10.1111\/crj.70035","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T05:38:56Z","timestamp":1733204336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting HLA\u2010E in Lung Cancer: The Therapeutic Potential of IRF5\u2010Engineered M1\u2010Macrophage\u2010Derived Exosomes"],"prefix":"10.1111","volume":"18","author":[{"given":"Xuqin","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Oncology Beijing Anzhen Nanchong Hospital, Capital Medical University (Nanchong Central Hospital), The Second Clinical Medical College of North Sichuan Medical College  Nanchong Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangyu","family":"Lai","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of 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