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.