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To investigate transcriptomic changes, we performed single-cell RNA sequencing (scRNA-seq) of treated and untreated tumors, and healthy tissues. CDK4\/6i-mediated TEC cycle arrest promoted arterial-venous specification, cellular junctions, and pericyte association, and suppressed glycolytic and immunosuppressive gene expression. These effects were associated with increased vessel perfusion, decreased tumor hypoxia, and a more favorable immune landscape with immunotherapy. In scRNA-seq datasets from patients treated long-term with CDK4\/6i, TECs exhibited similar transcriptomic changes associated with arterial-venous specification, pericyte recruitment, and immune signaling. 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