Checkpoint Breaches: Unexpected Effects of Anti–PD-1 Therapy on the Blood–Brain Barrier

Immune checkpoint inhibitors have revolutionized cancer therapy, and their unintended side effects relate largely to inducing autoimmunity; effects on vascular functions have only rarely been observed so far. In this issue of Cancer Discovery, a puzzling finding is reported that has divergent clinical implications: PD-1 inhibitors make cytotoxic T lymphocytes secrete a Wnt pathway suppressor to the blood that opens the blood-brain barrier, both allowing circulating tumor cells to enter the brain and a chemotherapeutic to better reach tumor cells in brain metastases. See related article by Deo et al., p. 976.