Bidirectional roles of meningeal lymphatic vessels in brain metastases: friend and foe.

Brain metastases constitute the most prevalent intracranial malignancies. Despite recent therapeutic advances, patient prognoses remain poor, largely due to significant treatment resistance and a highly restrictive tumor microenvironment. The rediscovery of meningeal lymphatic vessels (MLVs) has provided new insights into how the brain interacts with the immune system. MLVs are responsible for cerebrospinal fluid drainage, waste clearance, and immune cell trafficking, and their dysfunction is linked to many neurological diseases. In brain metastases, MLVs play a dynamic, dual role based on the evolving tumor microenvironment. Under physiological conditions or in early stages, MLVs promote anti - tumor immunity by draining tumor antigens to cervical lymph nodes and supporting T-cell activation. However, as the tumor progresses, excessive tumor - derived factors like VEGF-C cause pathological MLV remodeling. This structural change is a critical switch: pathologically dilated MLVs facilitate tumor dissemination and their drainage dysfunction creates a local immunosuppressive niche, leading to immune evasion. This "friend and foe" character makes MLVs a potential therapeutic target. Enhancing MLV drainage may improve immunotherapy and drug delivery, while inhibiting tumor-driven lymphangiogenesis may help limit metastatic spread. In this review, we summarize current knowledge on MLV biology, their interactions with brain metastases, and discuss potential strategies and challenges for targeting MLVs in future therapies.