Tumour vessel normalization and immune checkpoint blockade: a new synergism.

Abstract

Immune checkpoint inhibitors have emerged as potent immunotherapies for a variety of cancers.1 However, their effectiveness would be enhanced by facilitating T-cell trafficking into solid tumours, which in turn requires functional improvement of the angiogenic vasculature. Abnormal tumour vessels are unable to sustain adequate blood flow, thus potentiating tumour hypoxia and limiting drug and immune cell access. ‘Normalizing’ tumour vessels has emerged as a promising approach to enhance tumour perfusion by increasing vessel organization and coverage of endothelial cells by pericytes.2 However, lack of mechanistic insights and inability to induce durable effects have hampered clinical translation of vessel normalization. While it is unknown whether pre-existing normalized vessels could be a marker for therapeutic efficacy, Tian et al.3 in their recent publication in Nature, demonstrate the prognostic value of a ‘vessel normalization’ signature in cancer. Furthermore, they show a crucial role of interferon gamma (IFNγ)-producing Type1 T helper (Th1) cells in tumour vessel normalization, which can be further potentiated by immune checkpoint blockade. This is an exciting finding, which links immune checkpoint therapy and vascular normalization, and thus reveals a new synergy with diagnostic and therapeutic implications.