title: Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity.
abstract: Contemporary approaches for vaccination and immunotherapy are often capable of eliciting strong T-cell responses against tumor antigens. However, such responses are not parallel to clinical tumor regression. The development of evasion mechanisms within tumor microenvironment may be responsible for poor therapeutic responses. We report here that constitutive or inducible expression of B7-H1, a B7 family molecule widely expressed by cancers, confers resistance to therapeutic anti-CD137 antibody in mice with established tumors. The resistance is accompanied with failure of antigen-specific CD8+ CTLs to destroy tumor cells without impairment of CTL function. Blockade of B7-H1 or PD-1 by specific monoclonal antibodies could reverse this resistance and profoundly enhance therapeutic efficacy. Our findings support that B7-H1/PD-1 forms a molecular shield to prevent destruction by CTLs and implicate new approaches for immunotherapy of human cancers.
authors.affiliation: Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Hirano
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kaneko
authors.forename: Hideto
authors.initials: H
authors.lastname: Tamura
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong
authors.forename: Shengdian
authors.initials: S
authors.lastname: Wang
authors.forename: Masao
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rietz
authors.forename: Dallas B
authors.initials: DB
authors.lastname: Flies
authors.forename: Julie S
authors.initials: JS
authors.lastname: Lau
authors.forename: Gefeng
authors.initials: G
authors.lastname: Zhu
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000954:Antigens, Surface / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D060890:B7-H1 Antigen; D017635:Clonal Anergy; D005260:Female; D007167:Immunotherapy / Q000379:methods; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor