Endothelial cell cycle inhibition enables blood vessel maturation to normalize the tumor vasculature [scRNA-seq]

However, current approaches to normalize the tumor vasculature have limited efficacy. Palbociclib, an FDA-approved cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has beneficial effects on tumor and immune cells, but its impact on tumor vasculature is unknown.

In our studies, murine mammary tumor ECs (TECs) exhibited disrupted cell cycle control and impaired specification, and CDK4/6i treatment promoted TEC cycle control, enabling improved tumor vascular structure and function. To gain mechanistic insight, we performed scRNAseq that showed CDK4/6i-mediated TEC cycle arrest promoted arterial-venous specification, EC junctions, and pericyte recruitment, and suppressed genes regulating glycolysis and immunosuppressive signaling.