Targeting the tumor vasculature to enhance T cell activity

Highlights

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  Tumor vessels form a physical barrier that hampers intratumoral T cell trafficking.

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  Tumor endothelial cells can directly kill T cells or suppress their activity.

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  Normalization of the tumor endothelial barrier enhances T cell infiltration and activity.

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  Tumor vascular targeting synergizes with active and adoptive immunotherapies.

Abstract

T cells play a critical role in tumor immune surveillance as evidenced by extensive mouse-tumor model studies as well as encouraging patient responses to adoptive T cell therapies and dendritic cell vaccines. It is well established that the interplay of tumor cells with their local cellular environment can trigger events that are immunoinhibitory to T cells. More recently it is emerging that the tumor vasculature itself constitutes an important barrier to T cells. Endothelial cells lining the vessels can suppress T cell activity, target them for destruction, and block them from gaining entry into the tumor in the first place through the deregulation of adhesion molecules. Here we review approaches to break this tumor endothelial barrier and enhance T cell activity.