Targeting PD-1 and PD-L1 in Lung Cancer

Roy S. Herbst, MD, PhD, a professor of medicine at the Yale Cancer Center and chief of medicaloncology at Smilow Cancer Hospital at Yale-New Haven in Connecticut, discusses targeting PD-1 and PD-L1 when treating patients with lung cancer.

Tumors that express PD-L1 are generally resistant to the immune system, since PD-L1 binds to PD-1 on T cells to suppress immune activation. As a result, inhibiting PD-1 prevents the suppression of the immune system by blocking PD-1 and PD-L1 interaction, Herbst says. However, blocking PD-1 prevents interaction with both PD-L1 and PD-L2, a similar type of protein found on normal cells that regulates inflammation.

Researchers are concerned that blocking PD-L2 interaction may be increase toxicity. Following this logic, since treatments that block PD-L1 leave PD-1 available to bind to PD-L2, they may result in less toxicity. However, more data is still required to confirm this hypothesis, Herbst notes.

Clinical Pearls

• A tumor is resistant to the immune system because PD-L1, a protein that is found on normal immune cells that binds to PD-1 on the T cell, is also found on the cancer cells
• By blocking PD-1, the interaction between PD-1 and PD-L1 is blocked on the T cell side and causes the PD-1 to be unavailable to bind to PD-L2
• Physicians are concerned that by blocking the PD-1 and PD-L2 interaction, there may be increased toxicity.