title: Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.
abstract: B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in the regulation of cellular and humoral immune responses through the PD-1 receptor on activated T and B cells. We report here that, except for cells of the macrophage lineage, normal human tissues do not express B7-H1. In contrast, B7-H1 is abundant in human carcinomas of lung, ovary and colon and in melanomas. The pro-inflammatory cytokine interferon-gamma upregulates B7-H1 on the surface of tumor cell lines. Cancer cell-associated B7-H1 increases apoptosis of antigen-specific human T-cell clones in vitro, and the apoptotic effect of B7-H1 is mediated largely by one or more receptors other than PD-1. In addition, expression of B7-H1 on mouse P815 tumor increases apoptosis of activated tumor-reactive T cells and promotes the growth of highly immunogenic B7-1(+) tumors in vivo. These findings have implications for the design of T cell-based cancer immunotherapy.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
authors.forename: Diva R
authors.initials: DR
authors.lastname: Salomao
authors.forename: Hideto
authors.initials: H
authors.lastname: Tamura
authors.forename: Fumiya
authors.initials: F
authors.lastname: Hirano
authors.forename: Dallas B
authors.initials: DB
authors.lastname: Flies
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Roche
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Gefeng
authors.initials: G
authors.lastname: Zhu
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism*; D060890:B7-H1 Antigen; D001798:Blood Proteins; D002469:Cell Separation; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D019139:Tumor Escape; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C423236:CD274 protein, human; C498919:Cd274 protein, mouse; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha