Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity.
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.
Hirano
Fumiya
F
Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Kaneko
Katsumi
K
Tamura
Hideto
H
Dong
Haidong
H
Wang
Shengdian
S
Ichikawa
Masao
M
Rietz
Cecilia
C
Flies
Dallas B
DB
Lau
Julie S
JS
Zhu
Gefeng
G
Tamada
Koji
K
Chen
Lieping
L
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
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