Mucosal immunity in cancer metastasis: roles, mechanisms, and therapeutic implications

Previous studies have shown that the mucosal immune system plays a crucial role in regulating immune tolerance, maintaining the integrity of the mucosal barrier, and facilitating immune communication between organs. However, its role in tumor metastasis has not been fully investigated. This review integrates recent studies on mucosal immunity and tumor metastasis, systematically discussing the process by which mucosal immune dysregulation promotes tumor metastasis. We elucidate how the mucosal imprinting program formed within the common mucosal immune system affects metastasis through regulating immune tolerance, tissue-specific homing, and the circulating adaptability of metastatic tumor cells. During this process, the microbiota within the tumor also plays an important synergistic role. Through major mucosal axes such as the gut-lung axis and the gut-liver axis, damaged mucosal immunity remodels the composition and metabolic state of tissue-resident immune cells and remotely regulates the pre-metastatic microenvironment. At the distal mucosal sites, immune populations such as alveolar macrophages and tissue-resident memory T cells inhibit tumor metastasis growth by forcing tumor dormancy, maintaining mucosal immune balance. However, when the body experiences a chronic infection and the mucosal immune system is disrupted, dormant tumor cells can be reactivated for metastasis. This review describes the roles of mucosal immunity at different stages of tumor metastasis, providing a reference for understanding the role of mucosal immunity in tumor metastasis and revealing the key mechanism pathways and therapeutic strategies for preventing metastasis recurrence.