Blank Christian, Gajewski Thomas F, Mackensen Andreas
Department of Hematology and Oncology, University of Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany.
Cancer Immunol Immunother. 2005 Apr;54(4):307-14. doi: 10.1007/s00262-004-0593-x. Epub 2004 Dec 15.
Programmed death receptor ligand 1 (PD-L1, also called B7-H1) is a recently described B7 family member. In contrast to B7-1 and B7-2, PD-L1 does not interact with either CD28 or CTLA-4. To date, one specific receptor has been identified that can be ligated by PD-L1. This receptor, programmed death receptor 1 (PD-1), has been shown to negatively regulate T-cell receptor (TCR) signaling. Upon ligating its receptor, PD-L1 has been reported to decrease TCR-mediated proliferation and cytokine production. PD-1 gene-deficient mice developed autoimmune diseases, which early led to the hypothesis of PD-L1 regulating peripheral tolerance. In contrast to normal tissues, which show minimal surface expression of PD-L1 protein, PD-L1 expression was found to be abundant on many murine and human cancers and could be further up-regulated upon IFN-gamma stimulation. Thus, PD-L1 might play an important role in tumor immune evasion. This review discusses the currently available data concerning negative T-cell regulation via PD-1, the blockade of PD-L1/PD-1 interactions, and the implications for adoptive T-cell therapies.
程序性死亡受体配体1（PD-L1，也称为B7-H1）是最近发现的一种B7家族成员。与B7-1和B7-2不同，PD-L1既不与CD28也不与CTLA-4相互作用。迄今为止，已鉴定出一种可被PD-L1结合的特异性受体。该受体即程序性死亡受体1（PD-1），已被证明可负向调节T细胞受体（TCR）信号传导。据报道，PD-L1与其受体结合后，可减少TCR介导的增殖和细胞因子产生。PD-1基因缺陷小鼠会发生自身免疫性疾病，这一现象早期促使人们提出了PD-L1调节外周免疫耐受的假说。与正常组织中PD-L1蛋白表面表达极少不同，在许多小鼠和人类癌症中发现PD-L1表达丰富，且在γ干扰素刺激后可进一步上调。因此，PD-L1可能在肿瘤免疫逃逸中发挥重要作用。本文综述了目前有关通过PD-1进行负向T细胞调节、阻断PD-L1/PD-1相互作用以及对过继性T细胞疗法影响的现有数据。
