Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade.
PD-1 is a receptor of the Ig superfamily that negatively regulates T cell antigen receptor signaling by interacting with the specific ligands (PD-L) and is suggested to play a role in the maintenance of self-tolerance. In the present study, we examined possible roles of the PD-1/PD-L system in tumor immunity. Transgenic expression of PD-L1, one of the PD-L, in P815 tumor cells rendered them less susceptible to the specific T cell antigen receptor-mediated lysis by cytotoxic T cells in vitro, and markedly enhanced their tumorigenesis and invasiveness in vivo in the syngeneic hosts as compared with the parental tumor cells that lacked endogenous PD-L. Both effects could be reversed by anti-PD-L1 Ab. Survey of murine tumor lines revealed that all of the myeloma cell lines examined naturally expressed PD-L1. Growth of the myeloma cells in normal syngeneic mice was inhibited significantly albeit transiently by the administration of anti-PD-L1 Ab in vivo and was suppressed completely in the syngeneic PD-1-deficient mice. These results suggest that the expression of PD-L1 can serve as a potent mechanism for potentially immunogenic tumors to escape from host immune responses and that blockade of interaction between PD-1 and PD-L may provide a promising strategy for specific tumor immunotherapy.
Iwai
Yoshiko
Y
Department of Medical Chemistry, Graduate School of Medicine, Japan Science and Technology Corporation, Kyoto 606-8501, Japan.
Ishida
Masayoshi
M
Tanaka
Yoshimasa
Y
Okazaki
Taku
T
Honjo
Tasuku
T
Minato
Nagahiro
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; D007167:Immunotherapy; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins / Q000276:immunology; D017634:Self Tolerance; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins