Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances

Brain tumors, including primary intracranial tumors and brain metastases (BrMs), represent a major threat to human health and are associated with extremely poor prognoses. The brain tumor microenvironment (BTME) is a complex ecosystem composed of various elements, including tumor cells, immune cells, neurons, the vascular system, the extracellular matrix, and cytokines. These elements not only coexist spatially but are also functionally connected, interacting through intricate networks that collectively influence tumor initiation, progression, and therapeutic efficacy. In recent years, the application of novel technologies such as single-cell and spatial transcriptomics has uncovered complex cellular heterogeneity and spatial organization within the BTME. This review comprehensively summarizes the key components and functions of the BTME in tumor development and therapy, the mechanisms underlying intercellular interactions, with an emphasis on their clinical potential and challenges.