Arteriolar angiogenesis: implications in anti-angiogenic immunotherapy for pancreatic cancers

Angiogenesis, the newly formed blood vessels from preexistent ones, is essential for the progression and potential resolution of diseases. Here we introduce a view of arteriolar angiogenesis (the growth of new small arteries), and define a concept that molecular signaling balance between pro- and anti-angiogenic signaling determines angiogenic phenotype. We discuss VEGF and CXCL12 signaling pathways in vascular endothelial cells essential for arteriolar angiogenesis, which is potentially regulated by PKD1-mediated Notch1-CD36 signaling, emphasizing the function of arteriolar angiogenesis as a vascular niche/microenvironment under pathological conditions. We delineate implications of arteriolar angiogenesis in cancer stem cell development and anti-angiogenic immunotherapeutic strategies, highlighting anti-angiogenic strategy in combination with immune checkpoint blockade in pancreatic cancers. In summary, this review article seeks to develop the concept of arteriolar angiogenesis and yield insights into developing novel vascular targeting and immune therapies to cure cancers and cardiovascular and neurovascular diseases manifested with abnormal angiogenesis.