title: A soluble form of CD80 enhances antitumor immunity by neutralizing programmed death ligand-1 and simultaneously providing costimulation.
abstract: Tumor cells use various methods of immunosuppression to overcome antitumor immunity. One such method is that of programmed death ligand-1 (PD-L1 or B7-H1), which upon binding its receptor PD-1 on T cells triggers apoptotic death of the activated T cells. Overexpression of the costimulatory molecule CD80 on PD-L1(+) tumor cells, or inclusion of a soluble form of CD80 (CD80-Fc), maintains the activation of PD-1(+)-activated T cells. Using T cells from CD28-deficient mice and antibodies to block CD28 on human T cells, we now report that a soluble form of CD80 mediates this effect by simultaneously neutralizing PD-1-PD-L1-mediated immunosuppression and by providing CD80-CD28 costimulation, and is more effective than antibodies to PD-L1 or PD-1 in maintaining IFNγ production by PD-1(+) activated T cells. Therefore, soluble CD80 may be a more effective therapeutic than these checkpoint antibodies for facilitating the development and maintenance of antitumor immunity because it has the dual functions of preventing PD-L1-mediated immunosuppression and simultaneously delivering the second signal for T-cell activation.
authors.affiliation: Authors' Affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Haile
authors.affiliation: Authors' Affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland.
authors.forename: Lucas A
authors.initials: LA
authors.lastname: Horn
authors.affiliation: Authors' Affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland srosenbe@umbc.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ostrand-Rosenberg
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000172:deficiency / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D018106:CD28 Antigens