title: B7-H1 signaling is integrated during CD8(+) T cell priming and restrains effector differentiation.
abstract: A promising strategy in tumor immunotherapy is the use of activated dendritic cells as vehicles for tumor vaccines with the goal of activating anti-tumor T cell responses. Current formulations for dendritic cell-based immunotherapies have limited effects on patient survival, providing motivation for further investigation of ways to enhance dendritic cell priming of anti-tumor T cell responses. Using a brief in vitro priming model, we have found that B7-H1 expressed by activated dendritic cells is integrated during priming of naïve CD8(+) T cells and functions to limit the differentiation of effector T cell responses. CD8(+) T cells primed by B7-H1-deficient dendritic cells exhibit increased production of IFN-γ, enhanced target cell killing, and improved anti-tumor activity. Additionally, enhanced memory populations arise from CD8(+) T cells primed by B7-H1-deficient dendritic cells. Based on these findings, we suggest that early blockade of B7-H1 signaling should be investigated as a strategy to improve dendritic cell-based anti-tumor immunotherapy.
authors.affiliation: Biology Discipline, University of Minnesota, Morris, MN, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Gibbons
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Susan M
authors.initials: SM
authors.lastname: Harrington
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Krco
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Kwon
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
chemical_list: D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D019496:Cancer Vaccines; C498919:Cd274 protein, mouse