| First Author | Haile ST | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 5 | Pages | 2829-36 |
| PubMed ID | 23918985 | Mgi Jnum | J:205796 |
| Mgi Id | MGI:5546463 | Doi | 10.4049/jimmunol.1202777 |
| Citation | Haile ST, et al. (2013) Soluble CD80 restores T cell activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression. J Immunol 191(5):2829-36 |
| abstractText | Many tumor cells escape anti-tumor immunity through their expression of programmed death ligand-1 (PDL1 or B7-H1), which interacts with T cell-expressed PD1 and results in T cell apoptosis. We previously reported that transfection of human tumor cells with a membrane-bound form of the human costimulatory molecule CD80 prevented PD1 binding and restored T cell activation. We now report that a membrane-bound form of murine CD80 similarly reduces PDL1-PD1-mediated suppression by mouse tumor cells and that a soluble protein consisting of the extracellular domains of human or mouse CD80 fused to the Fc domain of IgG1 (CD80-Fc) overcomes PDL1-mediated suppression by human and mouse tumor cells, respectively. T cell activation experiments with human and mouse tumor cells indicate that CD80-Fc facilitates T cell activation by binding to PDL1 to inhibit PDL1-PD1 interactions and by costimulating through CD28. CD80-Fc is more effective in preventing PD1-PDL1-mediated suppression and restoring T cell activation compared with treatment with mAb to either PD1 or PDL1. These studies identify CD80-Fc as an alternative and potentially more efficacious therapeutic agent for overcoming PDL1-induced immune suppression and facilitating tumor-specific immunity. |
