Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade
Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade
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DOI：
10.1073/pnas.192461099
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发表时间：
2002-09-17
影响因子：
11.1
通讯作者：
Minato, N
中科院分区：
文献类型：
--
作者：
Iwai, Y;Ishida, M;Minato, N
PD-1是IG超家族的受体，其通过与特异性配体（PD-L）相互作用来负调节T细胞抗原受体信号传导，并且被认为在维持自身耐受性中起作用。在本研究中，我们研究了PD-1/PD-L系统在肿瘤免疫中的可能作用。PD-L 1基因在P815肿瘤细胞中的转基因表达使其在体外对特异性T细胞抗原受体介导的细胞毒性T细胞裂解的敏感性降低，并显著增强其在同基因宿主中的体内成瘤性和侵袭性。抗PD-L1抗体可逆转上述两种效应。鼠肿瘤系的调查显示，所有检测的骨髓瘤细胞系均天然表达PID-L1。正常同基因小鼠中骨髓瘤细胞的生长通过体内施用抗PD-L1 Ab而被显著抑制，尽管是短暂的，并且在同基因PD-1缺陷小鼠中被完全抑制。这些结果表明，PD-L1的表达可以作为潜在免疫原性肿瘤逃避宿主免疫应答的有效机制，并且阻断PD-1和PD-L之间的相互作用可以为特异性肿瘤免疫治疗提供有希望的策略。
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 PID-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.