Programmed death-ligand 1 (PD-L1) and CD80 (B7-1) (PD-L1/CD80)

Programmed death-ligand 1 (PD-L1) and CD80 (B7-1) are critical immune checkpoint ligands that interact in cis on the surface of antigen-presenting cells (APCs) and tumor cells to form a functional heterodimer. This interaction is biologically significant because it prevents PD-L1 from binding to its inhibitory receptor, PD-1, and simultaneously blocks CD80 from interacting with the inhibitory receptor CTLA-4, while crucially preserving the ability of CD80 to provide costimulatory signals through CD28 (Zhao et al., 2019; Sugiura et al., 2019). By sequestering these inhibitory ligands, the PD-L1:CD80 complex acts as a natural rheostat that facilitates optimal T-cell activation and prevents premature immune exhaustion in the tumor microenvironment (Zhao et al., 2019). Additionally, this interaction has been shown to play a role in the chemokine-driven migration of dendritic cells to lymph nodes (Kantheti et al., 2025). Therapeutically, the PD-L1:CD80 interaction is a major focus for next-generation immunotherapies, including CD80-Fc fusion proteins like davoceticept and bispecific antibodies like IBI318, which aim to exploit or stabilize this complex to enhance anti-tumor immunity (Alpine Immune Sciences, 2022; OncLive, 2014). However, the disruption of this interaction by certain standard PD-L1 inhibitors, such as atezolizumab, can paradoxically lead to the depletion of CD80 from the cell surface, potentially limiting efficacy unless combined with CTLA-4 blockade (Zhao et al., 2019). Clinical development of agents targeting this complex has faced significant safety challenges, most notably fatal cardiac events such as myocarditis and cardiogenic shock observed in trials combining davoceticept with PD-1 inhibitors (Alpine Immune Sciences, 2022; JITC, 2024).

Other names

PD-L1:CD80 cis-heterodimerB7-H1 and B7-1 complexCD274 and CD80 interactionPD-L1/B7-1 interaction

Blockade of PD-L1:PD-1 and PD-L1:CD80 interactions to prevent T-cell inhibition; stabilization of the PD-L1:CD80 cis-heterodimer to promote CD28-mediated costimulation; and prevention of CTLA-4-mediated trans-endocytosis of CD80.