PD-L1

PD-L1 is a transmembrane protein expressed on dendritic cells, macrophages, and many tumors. Its outer domain engages PD-1 on T cells to form an inhibitory synapse. The interaction recruits the SHP2 phosphatase, dampening T-cell receptor signaling and preventing over-activation. Interferons, hypoxia, and oncogenic pathways like MYC or EGFR push PD-L1 levels upward, while vesicles can ferry it to distant cells. Checkpoint inhibitors are simply high-affinity binders that wedge between PD-L1 and PD-1. Designing new binders with refined epitopes or effector functions helps teams reopen exhausted T cells, overcome resistance pathways, and tailor immunotherapy for stubborn tumors.