New answers on PD-L1
HOUSTON—Recent work from scientists at MD Anderson Cancer Center, led by Dr. Mien-Chie Hung, chair of Molecular and Cellular Oncology, has uncovered new insight into how PD-L1 suppresses the immune system. The team found a previously unknown immunosuppression mechanism in cancer cells: inhibition of protein CSN5 activity blocked PD-L1’s ability to avoid the immune system. Specifically, CSN5 affects PD-L1’s interaction with PD-1, a cell receptor that blocks T cell activation when it binds with PD-L1. TNFa was also found to impact CSN5’s ability to ‘stabilize’ PD-L1 and boost its interaction with PD-1.
“This regulatory event is critical for breast cancer cells to escape immune surveillance via interaction between PD-L1 and PD-1,” Hung explained. “Importantly, inhibition of TNFa-mediated PD-L1 stabilization in cancer cells promotes the tumor-infiltrating immune response. Thus, targeting cancer cell PD-L1 stabilization through CSN5 inhibition could help us develop better treatments for cancer accompanied by inflammation.”