Dopamine D2 receptor agonists inhibit lung cancer progression by reducing angiogenesis and tumor infiltrating myeloid derived suppressor cells

We sought to determine whether Dopamine D2 Receptor (D₂R) agonists inhibit lung tumor progression and identify subpopulations of lung cancer patients that benefit most from D₂R agonist therapy. We demonstrate D₂R agonists abrogate lung tumor progression in syngeneic (LLC1) and human xenograft (A549) orthotopic murine models through inhibition of tumor angiogenesis and reduction of tumor infiltrating myeloid derived suppressor cells. Pathological examination of human lung cancer tissue revealed a positive correlation between endothelial D₂R expression and tumor stage. Lung cancer patients with a smoking history exhibited greater levels of D₂R in lung endothelium. Our results suggest D₂R agonists may represent a promising individualized therapy for lung cancer patients with high levels of endothelial D₂R expression and a smoking history.