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

ABSTRACT: An immunosuppressive tumor microenvironment (TME) constrains therapeutic efficacy and worsens prognosis. 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. This redistribution was accompanied by peripheral enrichment of endothelial ICAM-1 and loss of vascular integrity. Functionally, ICAM-1 blockade restored intratumoral T-cell infiltration, enhanced effector activity, and significantly delayed tumor growth. Together, these findings identify endothelial ICAM-1 as a vascular determinant of T-cell positioning and highlight the ICAM-1/LFA-1 axis as a modifiable checkpoint to improve T-cell access to the tumor core and augment antitumor immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE319704 | GEO | 2026/09/18

REPOSITORIES: GEO

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