Quercetin inhibiting the <scp>PD</scp>‐1/<scp>PD‐L1</scp> interaction for immune‐enhancing cancer chemopreventive agent
Lei Jing, Jieru E. Lin, Yang Yang, Tao Li, Yuyin Li, Zhenxing Liu, Qing Zhao, Aipo Diao
Abstract
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.