Programmed cell death-1/programmed cell death ligand-1 checkpoint inhibitors: differences in mechanism of action

Programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors are widely used in many types of solid tumors, and are often considered to be in the same immunotherapy subclass. This review explores whether specific agents in these two categories exhibit differences in their mechanism of action, pharmacokinetics and pharmacodynamics, and clinical efficacy and safety. Due to the complicated functional pathways in the immune checkpoint system, the epitopes, interfaces and signal pathways between PD-1: PD-L1/PD-L2, PD-L1/CD28/CTLA-4: B7-1 axes often overlap and affect each other. Therefore, the mechanisms of action of PD-1 and PD-L1 inhibitors reflect the corresponding cross connectivity and their unique characteristics. Only head-to-head comparative studies can provide definitive information regarding clinical efficacy and safety differences between specific PD-1/PD-L1 inhibitors.