Blood vascular endothelial cells

• Endothelial cells (ECs) form a single cell layer that lines all blood vessels. Tumor ECs display a remarkable heterogeneity and plasticity, and they control the passage of proteins, cells, oxygen, and fluid into the surrounding tissue.

• ECs that line tumor blood vessels differ from normal ECs. Tumor ECs express lower levels of adhesion molecules, which causes an impaired barrier function, and they express increased levels of inhibitory immune checkpoint molecules, which contributes to immunosuppression.

Lymphatic ECs

• Lymphatic ECs (LECs) form the walls of lymphatic vessels. In the TME, lymphatic vessels provide a dissemination route for cancer cells in addition to blood vessels.

• LECs have recently also been recognized as direct regulators of anti-tumor immunity and immunotherapy response. LECs can present tumor antigens but also immune checkpoint molecules. Ma et al.348

Pericytes

• Pericytes, also known as mural cells, surround blood vessels and are embedded in the basement membrane of vessels and adjacent to ECs. They support the maturation and permeability of the vasculature.

• In tumors, an impaired interaction between pericytes and ECs contributes to a leaky and dysfunctional tumor vasculature.

• Pericytes also interact with other stromal cells and cancer cells via paracrine mechanisms, resulting in modulation of the TME. In particular, there is growing interest in the immunomodulatory activity of pericytes.