Immunomodulation of Tumor Vessels: It Takes Two to Tango

Abstract

The density of intratumoral CD8⁺ T cells predicts patient survival and responsiveness to immunotherapy. Effector T cell infiltration in turn is controlled by the tumor vasculature which co-evolves together with an immune-suppressive environment. At the T cell-vascular interface, endothelial cells actively suppress T cell trafficking and function. Conversely, forced activation, normalization, and differentiation of tumor vessels into high endothelial venule entrance portals for lymphocytes can facilitate T cell extravasation. Emerging evidence demonstrates that this process is not exclusively controlled by the endothelium. Indeed, tumor vasculature and CD4⁺ and/or CD8⁺ T cells may regulate each other: increasing local effector T cell numbers or re-invigorating pre-existing T cells via immune checkpoint blockade can directly affect the vasculature. A deeper understanding of the orchestration and duration of this reciprocal relationship may help shape the design of future immunotherapies.