T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels

To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating T cells preferably adhered and extravasated at a distinct type of venous blood vessel in the tumor vicinity, peritumoral venous vessels (PVVs). Other vascular structures were excluded as alternative T cell routes to intracranial melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors increased intracranial T cell motility, facilitating migration from PVVs to the tumor and subsequently inhibiting intracranial tumor growth. The endothelial adhesion molecule ICAM-1 was particularly expressed on PVVs, and, in samples of human brain metastases, ICAM-1 positivity of PVV-like vessels correlated with intratumoral T cell infiltration. These findings uncover a distinct mechanism by which the immune system can access and control brain tumors and potentially influence other brain pathologies. [Display omitted] •PVVs are key structures for T cell recruitment to melanoma brain tumors•Anti-PD-1/CTLA-4 inhibitors boost T cell recruitment through PVVs•T cell recruitment and antitumor immunity is dependent on ICAM-1 expression on PVVs•ICAM-1 on PVVs correlates with T cell infiltration in human melanoma brain metastases How T cells are recruited to brain tumors from the blood remains unclear. Messmer et al. identify peritumoral venous vessels (PVVs) as key structures for T cell recruitment to melanoma brain tumors. PVVs are the sites of T cell extravasation and facilitated rapid T cell migration under immune checkpoint inhibition. T cell recruitment and antitumor immunity were dependent on ICAM-1.