Figure 1.

The tumor microenvironment and the tumor endothelial cell barrier. (a). The tumor microenvironment is comprised of tumor cells, an aberrant vasculature lined by endothelial cells and supported by pericytes, stromal cells, an extracellular matrix, and a range of immune infiltrates including T cells, regulatory T cells (Treg), myeloid derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), fibroblasts and dendritic cells (DCs). (b) T cell extravasation is dependent upon endothelial cell expression of intracellular cell adhesion molecule-1 (ICAM-1) and vasculature cell adhesion molecule-1 (VCAM-1). Tumor derived angiogenic growth factors such as VEGF and endothelin-1 (ET-1) signal through their cognate receptors, VEGFR and ET_BR, respectively, to block the expression of adhesion molecules and inhibit T cell infiltration into the tumor bed. (c) The endothelium, under the influence of tumor-derived factors like VEGF, can directly inhibit T cell activation by upregulating inhibitory molecules such as PD-L1, PD-L2, IDO-1, IL-6, and IL-10, amongst many others. (d) Tumor endothelial cells can also express FasL which leads to apoptosis of Fas-expressing T cells.