Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade

Y Iwai, M Ishida, Y Tanaka, T Okazaki… - Proceedings of the …, 2002 - National Acad Sciences
Y Iwai, M Ishida, Y Tanaka, T Okazaki, T Honjo, N Minato
Proceedings of the National Academy of Sciences, 2002National Acad Sciences
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 …
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.
National Acad Sciences