Soluble CD80 Restores T Cell Activation and Overcomes Tumor Cell Programmed Death Ligand 1–Mediated Immune Suppression
| Autor: | Suzanne Ostrand-Rosenberg, Sonia P. Dalal, Koji Tamada, Samuel T. Haile, Virginia K. Clements |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 191:2829-2836 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1202777 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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