TGFBI in tumors and the tumor immune microenvironment: functional roles, mechanisms, and therapeutic targeting

TGFBI in tumors, providing a comprehensive theoretical foundation for developing TGFBI-based precision diagnosis and treatment. Transforming growth factor-beta-induced protein (TGFBI) is a secreted extracellular matrix protein involved in various physiological and pathological processes. Its multiple roles in tumorigenesis and the remodeling of the tumor immune microenvironment (TIME) have recently drawn increasing attention. This review systematically compares the dual pro-tumor and tumor-suppressive functions of TGFBI across multiple cancer types and provides a comprehensive analysis of its immunomodulatory roles-particularly its recently identified function as a secreted immune checkpoint bridging extracellular matrix remodeling and immune suppression. By integrating evidence from single-cell and spatial transcriptomic studies, we elucidate the cell-type-specific expression patterns of TGFBI in the tumor microenvironment and propose a tumor-type-specific therapeutic stratification framework for TGFBI-targeted interventions. This review thus fills a critical gap by providing the first systematic integration of TGFBI's context-dependent functions with its translational implications.