Peritumoral Venous Vessels: Autobahn and Portal for T Cells to Melanoma Brain Metastasis

Melanoma brain metastasis is associated with high morbidity and mortality and remains a major clinical challenge. Despite recent successes with combination immune checkpoint inhibitors in the treatment of affected patients, the mechanistic underpinnings of T-cell entry and response to these drugs in brain metastasis are poorly understood. Using real-time intravital microscopy, Messmer and colleagues identified peritumoral venous vessels (PVV) as critical sites for T-cell entry into brain metastases, a process accelerated by immune checkpoint inhibitor treatment. The expression of intercellular adhesion molecule 1 on PVVs was found to be important for T-cell recruitment in preclinical models and associated with increased T-cell infiltration in human brain metastatic lesions. This study highlights PVVs as key vascular entry points for T cells into brain metastases, laying the foundation for enhancing the efficacy of cancer immunotherapies.