The Interplay of Cross-Organ Immune Regulation in Inflammation and Cancer

Organs dynamically interact with each other through immunomodulation to create a systemic immune response and influence disease progression. While traditional studies have tended to focus on single-organ 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-organ 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-organ 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-on-a-chip 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-organ immunity.