Programmed death-ligand 1 – Cluster of differentiation 80 interaction (PD-L1–CD80 interaction)

Programmed death-ligand 1 (PD-L1, CD274) and Cluster of differentiation 80 (CD80, B7-1) interact physically in both *cis* (on the same cell) and, possibly less frequently, *trans* (across cells). This interaction occurs primarily on antigen-presenting cells (APCs), such as dendritic cells and macrophages, and modulates the availability of both proteins for canonical immune checkpoint pathways. When PD-L1 binds CD80 in *cis*, it reduces PD-L1’s ability to bind PD-1 and inhibit T cells, and also shields CD80 from interacting with CTLA-4, but not with CD28. This complex crosstalk acts as a rheostat governing immune activation and suppression, and is central to immune checkpoint blockade therapies in cancer and autoimmune disease. Therapies that disrupt PD-L1:PD-1 (but not PD-L1:CD80) can unleash antitumor immunity, while drugs and mutations that specifically affect PD-L1:CD80 interaction are under research for their unique modulatory properties on the immune response. The molecular biology of PD-L1–CD80 interaction is nuanced and debated, but strong evidence supports its role as a critical modulator of immunotherapy response in cancer as well as autoimmune conditions. PD-L1 and CD80 are both B7 family proteins and can be differentially expressed and regulated on immune cells and some tumor cells. CD80 also interacts with CD28 (costimulatory) and CTLA-4 (coinhibitory), so the PD-L1–CD80 link is a point of convergence for multiple checkpoint and co-signaling pathways. Current clinical biomarker use typically involves PD-L1 and CD80 immunohistochemistry, but nuanced analysis of “free” versus “bound” PD-L1 is emerging due to these insights.

Other names

PD-L1:CD80CD274–CD80 interactionB7-H1–B7-1 interactionProgrammed cell death 1 ligand 1–CD80 interaction

Blockade of PD-L1 binding to PD-1 (immune checkpoint inhibition); Disruption of PD-L1:CD80 interaction (*cis* or *trans*) to modulate T cell activation; Augmentation or suppression of antitumor immunity via changing immune coinhibitory/costimulatory balance