Programmed cell death 1 ligand 1 and CD80 antigen interaction (PD-L1/CD80)

The interaction between Programmed cell death 1 ligand 1 (PD-L1) and CD80 (B7-1) is a critical regulatory axis within the immune checkpoint landscape that modulates T-cell activation (Sugiura et al., 2019). Unlike the well-characterized trans-interaction between PD-L1 on tumor cells and PD-1 on T-cells, the PD-L1/CD80 interaction often occurs in cis on the same cell membrane, such as on antigen-presenting cells or tumor cells (Chaudhri et al., 2018). This cis-binding sequesters both PD-L1 and CD80, preventing PD-L1 from engaging the inhibitory receptor PD-1 and simultaneously preventing CD80 from providing necessary costimulatory signals through CD28 (UniProt P20963). In the context of oncology, this interaction can limit the availability of CD80 for T-cell priming, thereby facilitating immune evasion by the tumor. Therapeutic monoclonal antibodies like atezolizumab and durvalumab target the PD-L1 binding interface, disrupting the PD-L1/CD80 complex and releasing CD80 to interact with CD28 (Butte et al., 2007). This disruption is thought to enhance the anti-tumor immune response by combining the relief of PD-1 mediated inhibition with the restoration of CD28-mediated costimulation. Consequently, the PD-L1/CD80 axis is a significant factor in the efficacy of current immunotherapies and remains a focal point for developing next-generation checkpoint inhibitors (PubMed: 31142640).

Other names

B7-H1/B7-1 interactionCD274/CD80 interactionPD-L1:CD80 cis-heterodimerPD-L1:CD80 complex

Disruption of the PD-L1/CD80 interaction to prevent PD-1/PD-L1 inhibitory signaling and restore CD80/CD28 costimulatory signaling.