title: Soluble CD80 restores T cell activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Haile
authors.forename: Sonia P
authors.initials: SP
authors.lastname: Dalal
authors.forename: Virginia
authors.initials: V
authors.lastname: Clements
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ostrand-Rosenberg
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology* / Q000378:metabolism; D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen; D060890:B7-H1 Antigen
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