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While traditional studies have tended to focus on single\u2010organ immunity, recent studies have placed greater emphasis on reciprocal immune interactions between organs, such as those between the gut, liver, and brain. However, the precise mechanisms underlying these interorgan immune interactions remain unclear. Here, we synthesize the molecular and cellular bases of cross\u2010organ immune regulation in the context of inflammation and neoplasia. Specifically, we describe the immune coordination between the gut, liver, and brain and how they immunomodulate other organs (including the thyroid, lung, cardiovascular system, kidney, bone, and skin). In addition, we explore clinical therapies that target these cross\u2010organ immune modulations, the limitations of the treatments, and the potential benefits for patients. We also conclude by highlighting innovative technologies such as multiomics analysis, machine learning, and organ\u2010on\u2010a\u2010chip platforms, which are providing unprecedented insights into interorgan immunity. Elucidating these mechanisms will advance precision medicine and enable the development of targeted therapies for diseases caused by cross\u2010organ immunity.<\/jats:p>","DOI":"10.1002\/mco2.70249","type":"journal-article","created":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T23:59:17Z","timestamp":1750031957000},"source":"Crossref","is-referenced-by-count":8,"title":["The Interplay of Cross\u2010Organ Immune Regulation in Inflammation and Cancer"],"prefix":"10.1002","volume":"6","author":[{"given":"Jie","family":"Dou","sequence":"first","affiliation":[{"name":"Department of General Surgery Sir Run\u2010Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzuo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Hangzhou Institute for Advanced Study 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