Short communicationHedgehog signaling regulates PDL-1 expression in cancer cells to induce anti-tumor activity by activated lymphocytes

•Hypoxia induces PDL-1 expression and activates Hedgehog (Hh) signaling in cancer.•Hh signaling inhibitor suppresses PDL-1 expression in cancer cells under hypoxia.•Hh signaling inhibitor increases anti-tumor effect of activated lymphocytes.•Hh signaling inhibitor is a useful molecular targeting drug as a PDL-1 inhibitor.

We investigated whether hypoxia-induced activation of Hh signaling contributes to PDL-1 expression in cancer and whether it affects the anti-tumor function of activated lymphocytes. Hypoxia augmented PDL-1 expression and inhibition of Hh signaling reduced PDL-1 expression under hypoxia. When activated lymphocytes were cocultured with cancers treated with a Hh inhibitor, activated lymphocyte cell numbers increased under hypoxia. In contrast, this increase was abrogated when cancer cells were treated with a PDL-1 neutralizing antibody. These results suggest that Hh signaling is one of regulatory pathways of PDL-1 expression under hypoxia and that inhibiting Hh signaling may induce lymphocyte anti-tumor activity.