Role of hypoxia in inhibiting dendritic cells by VEGF signaling in tumor microenvironments: mechanism and application

The tumor microenvironment (TME) plays a central role in tumor initiation, development, immune escape, and clinical treatment. Hypoxia, an important characteristic of the TME, mediates vascular endothelial factor (VEGF) signaling through direct or indirect mechanisms. Directly, hypoxia promotes the expression of VEGF through hypoxia-inducible factor (HIF) induction. Indirectly, VEGF inhibits dendritic cell (DC) maturation and function by binding to VEGF receptors (VEGFRs) and co-receptors expressed on cell membranes. Additionally, HIF can bypass VEGF/ VEGFR and activate downstream signaling factors to promote tumor development. Currently, DC vaccine, anti-HIF and anti-VEGF therapies are widely used in clinical treatment, but their long-term effects remain limited. Therefore, a further understanding of the effects of hypoxia and VEGF signaling on DCs will help in the development of innovative combination therapies and the identification of new targets.