VEGF neutralization alters the innate immune cell compartment and enhances intratumoral T cell activation (TUM10P.1040)

Although targeting the vascular endothelial growth factor (VEGF) pathway has been used in clinic as an anti-angiogenic therapy to combat cancer for almost a decade, the precise mechanisms of action have yet to be fully defined. Here we demonstrate in a panel of syngeneic tumor models that in addition to it’s anti-angiogenic activity, VEGF blockade augmented inflammation within tumors. Enhanced inflammation coincided with altered myeloid cell composition and modulation of dendritic cell activation. Modifications within the innate immune cell compartment mediated by anti-VEGF treatment correlated with enhanced functional capacity of tumor infiltrating T cells. This was characterized by increased cytokine production of total as well as antigen-specific T cells and decreased surface expression of negative immune regulators. VEGF receptors are detected on both innate immune cells and T cells suggesting that VEGF neutralization has a direct effect on these compartments. Based on these data, VEGF neutralization increased tumor inflammation by modulation of the innate immune cell compartment as well as promotion of anti-tumor T cell responses. Therefore, therapeutics that target the VEGF pathway have potential to work in concert with immunotherapeutics.