Center for Cancer Immune Therapy (CCIT), Department of Hematology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Drug Discov Today. 2015 Sep;20(9):1127-34. doi: 10.1016/j.drudis.2015.07.003. Epub 2015 Jul 17.
Physiologically, the programmed death 1 (PD-1) pathway is involved in limiting the killing of bystander cells during an infection and controlling autoimmunity. However, cancers exploit this system to avoid immune killing, and PD-1 ligand 1 and 2 (PD-L1 and PD-L2) expression on tumor cells, as well as PD-1 expression on tumor-infiltrating lymphocytes, have shown to be negative prognostic factors. Promising clinical results have been obtained by PD-1 pathway blockade in a range of cancers while still maintaining a manageable toxicity profile, and two anti-PD-1 antibodies are now approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma. As already shown with nivolumab and ipilimumab, the combination of PD-1 pathway blockade with other anticancer agents holds promise in the form of additive synergistic anticancer effects.
从生理学角度来看，程序性死亡 1（PD-1）途径参与限制感染过程中旁观者细胞的杀伤，并控制自身免疫。然而，癌症利用该系统来避免免疫杀伤，肿瘤细胞上的 PD-1 配体 1 和 2（PD-L1 和 PD-L2）表达以及肿瘤浸润淋巴细胞上的 PD-1 表达已被证明是负预后因素。在一系列癌症中通过 PD-1 途径阻断已获得有希望的临床结果，同时仍保持可管理的毒性特征，并且两种抗 PD-1 抗体现已被美国食品和药物管理局（FDA）批准用于治疗转移性黑色素瘤。如 nivolumab 和 ipilimumab 已经显示的那样，PD-1 途径阻断与其他抗癌药物的联合使用具有以附加协同抗癌作用的形式带来希望。
