Organ-Specific Migration License (OSML) theory: a novel paradigm for spatiotemporal regulation and intervention of cross-organ immune cell migration in tumor immune responses.

The efficacy of antitumor immune responses depends not only on the activation and effector function of local immune cells but also on the dynamic interplay between the tumor microenvironment and systemic immunity. Emerging evidence indicates that the migration of immune cells from tumor sites to secondary lymphoid organs and the circulatory system is essential for translating localized immune activity into systemic protective responses. This migratory process displays marked organ-specific spatial heterogeneity and temporal variability, which complicate the prediction and modulation of systemic outcomes through local therapeutic strategies.We propose the concept of Organ-Specific Migration Licensing (OSML) to delineate the mechanisms and biological underpinnings that govern immune cell trafficking in tumor immunity. This framework integrates spatial heterogeneity, temporal dynamics, and intervention-induced reprogramming to clarify how organ-specific factors shape immune efficacy and resistance. Crucially, these three dimensions are not independent but intricately coupled, forming a dynamic regulatory system that determines whether immune cells receive “migration permission”. The OSML paradigm advances tumor immunotherapy from a focus on local modulation to one of systemic coordination, offering a conceptual and practical foundation for optimizing organ-targeted combination therapies.