Vascular normalization as an emerging strategy to enhance cancer immunotherapy
Cette étude passe en revue les travaux récents sur le rôle du facteur de croissance de l'endothélium vasculaire dans le micro-environnement immunitaire des tumeurs et suggère une stratégie basée sur de faibles doses d'agents antiangiogéniques pour renforcer les effets des immunothérapies
The recent approval of Provenge has brought new hope for anti-cancer vaccine therapies. However, the immunosuppressive tumor microenvironment seems to impair the efficacy of vaccine therapies. The abnormal tumor vasculature creates a hypoxic microenvironment that polarizes inflammatory cells toward immune suppression. Moreover, tumors systemically alter immune cells' differentiation and their function via secretion of growth factors and cytokines. For example, vascular endothelial growth factor (VEGF), a major pro-angiogenic cytokine induced by hypoxia, plays a critical role in immunosuppression via these mechanisms. Hence, anti-angiogenic treatment may be an effective modality to potentiate immunotherapy. Here we discuss the local and systemic effects of VEGF on tumor immunity, and propose a potentially translatable strategy to re-engineer the tumor immune microenvironment and improve cancer immunotherapy by using lower "vascular normalizing" doses of anti-angiogenic agents.