Moy Ryan H, Younes Anas
Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Hemasphere. 2018 Feb 16;2(1):e20. doi: 10.1097/HS9.0000000000000020. eCollection 2018 Jan-Feb.
Intricate systems of checkpoints such as the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis regulate adaptive immune responses to protect against tissue damage. However, diverse cancers can exploit these pathways to evade or suppress antitumor immunity, leading to tumor progression. Correspondingly, immune checkpoint inhibitors that block PD-1/PD-L1 signaling have shown marked therapeutic efficacy in certain cancers, such as Hodgkin lymphoma. Reed-Sternberg cells, the hallmark cells of Hodgkin lymphoma, commonly overexpress PD-1 ligands, and recent clinical trials have demonstrated impressive response rates with the PD-1 inhibitors nivolumab and pembrolizumab in relapsed or refractory Hodgkin lymphoma, leading to their FDA approval in this setting. Current efforts are underway to improve clinical responses by incorporating PD-1 inhibitors into earlier treatment regimens and identifying therapeutic agents that synergize with PD-1 inhibitors. This review summarizes our understanding of the PD-1/PD-L1 axis in Hodgkin lymphoma, recent clinical studies of anti-PD-1 monotherapy and promising combination immunotherapy in the pipeline.
诸如程序性细胞死亡蛋白1(PD-1)/程序性死亡配体1(PD-L1)轴等复杂的检查点系统调节适应性免疫反应以防止组织损伤。然而,多种癌症可利用这些途径逃避免疫或抑制抗肿瘤免疫,导致肿瘤进展。相应地,阻断PD-1/PD-L1信号传导的免疫检查点抑制剂在某些癌症(如霍奇金淋巴瘤)中已显示出显著的治疗效果。里德-施特恩伯格细胞是霍奇金淋巴瘤的标志性细胞,通常过度表达PD-1配体,最近的临床试验表明,PD-1抑制剂纳武单抗和派姆单抗在复发或难治性霍奇金淋巴瘤中具有令人印象深刻的缓解率,从而导致它们在此情况下获得美国食品药品监督管理局(FDA)的批准。目前正在努力通过将PD-1抑制剂纳入更早的治疗方案以及确定与PD-1抑制剂协同作用的治疗药物来改善临床反应。本综述总结了我们对霍奇金淋巴瘤中PD-1/PD-L1轴的理解、抗PD-1单药治疗的最新临床研究以及即将进行的有前景的联合免疫治疗。