Quercetin inhibiting the PD-1/PD-L1 interaction for immune-enhancing cancer chemopreventive agent.

Targeting the PD-1/PD-L1 immune checkpoints has achieved significant positive results in the treatment of multiple cancers. Quercetin is one of the most abundant dietary flavonoids found in various vegetables and fruits, and has a wide range of biological activities including immunomodulation. Here we report that quercetin dihydrate was screened and shown to inhibit the PD-1/PD-L1 interaction. Treatment with quercetin dihydrate promoted the killing activity of T cells on MDA-MB-231 and NCI-H460 cancer cells. Experiments using the xenograft mouse model showed that the growth rate of tumor volumes and masses in the quercetin dihydrate-treated mice were decreased. Immunohistochemistry of the tumors showed that CD8, GZMB, and IFN-γ were increased in the quercetin dihydrate-treated mice. These results suggest that quercetin dihydrate attenuates the inhibitory effect of PD-L1 on T cells by inhibiting the PD-1/PD-L1 interaction, which has an exciting potential to be used as a cancer chemopreventive agent.