The vascular contribution to immunotherapy success

Angiogenesis represents a mechanism enabling tumors to evade immune surveillance. This immune escape is mediated, at least in part, by angiogenic factor-induced endothelial cell anergy, which suppresses leukocyte adhesion and infiltration into the tumor microenvironment. Consequently, it is becoming increasingly evident that the efficacy of immunotherapy can be improved by its combination with anti-angiogenic agents. Numerous studies, including clinical trials, have provided proof of this concept. A paper in this issue of Angiogenesis further substantiates this paradigm by demonstrating that normalizing the tumor vasculature and overcoming endothelial cell anergy also ameliorates the activity of CAR T cell therapy. Here, we place these findings into a broader mechanistic context and discuss their implications for combination treatment strategies.