Spatial polarization of endothelial ICAM-1 drives CD8⁺ T cell exclusion in melanoma [Xenium]

Beyond T-cell abundance and functionality, their spatial proximity to malignant cells is a critical determinant of tumor control. However, the vascular mechanisms that govern intratumoral T-cell positioning remain poorly defined.

Through RNA sequencing of endothelial cells isolated from tumor cores versus peripheries in a mouse melanoma model, we identified intercellular adhesion molecule 1 (ICAM-1) as a candidate regulator of T-cell localization. As tumors progressed, T cells shifted from a balanced core–margin distribution to pronounced core exclusion, coinciding with elevated lymphocyte function-associated antigen-1 (LFA-1) expression on T cells —a pattern less evident in other immune subsets.