Department of Medicine, University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL 60637 USA ; Committee on Immunology, University of Chicago, Chicago, IL USA.
Department of Medicine, University of Chicago, 5841 S. Maryland Ave., MC2115, Chicago, IL 60637 USA.
J Immunother Cancer. 2015 Jul 21;3:33. doi: 10.1186/s40425-015-0079-8. eCollection 2015.
Although cancer cells express antigens recognizable to the immune system, tumors employ a number of diverse mechanisms aimed at subverting the host anti-tumor immune response. Tumor immune evasion pathways have been most thoroughly studied in solid tumors. However, emerging data has demonstrated that malignancies of hematopoietic origin are also able to co-opt their local environment in order to escape immune attack. Activated T cells upregulate negative costimulatory receptors, such as programmed death-1 (PD-1) and cytotoxic lymphocyte antigen-4 (CTLA-4). Engagement of PD-1 or CTLA-4 with ligands expressed on tumor cells or professional antigen presenting cells results in down-regulation of effector T cell function and represents a potent mechanism of immune evasion across a number of human cancers. Antibodies which block PD-1 / PD-L1 interactions have demonstrated remarkable activity in a number of solid tumor subtypes. Interestingly, recent data have demonstrated that in select subtypes of Hodgkin (HL) and non-Hodgkin lymphoma (NHL), the PD-1 ligands are over-expressed due to a genetic amplification of the loci encoding them. Other mechanisms of PD-L1 over-expression in lymphoma have also been elucidated. Reports from early-phase clinical trials of PD-1 blockade have demonstrated remarkable effectiveness in HL, and also appear active against some NHLs. We review the mechanisms of PD-L1 expression in lymphoma and also the early results of anti-PD-1 therapy in this disease.
虽然癌细胞表达可被免疫系统识别的抗原，但肿瘤采用了许多不同的机制，旨在颠覆宿主的抗肿瘤免疫反应。肿瘤免疫逃逸途径在实体瘤中得到了最深入的研究。然而，新出现的数据表明，造血来源的恶性肿瘤也能够利用其局部环境来逃避免疫攻击。激活的 T 细胞上调负共刺激受体，如程序性死亡受体-1（PD-1）和细胞毒性淋巴细胞抗原-4（CTLA-4）。PD-1 或 CTLA-4 与肿瘤细胞或专业抗原呈递细胞上表达的配体结合，导致效应 T 细胞功能下调，这是许多人类癌症中一种有效的免疫逃逸机制。阻断 PD-1/PD-L1 相互作用的抗体在许多实体瘤亚型中显示出显著的活性。有趣的是，最近的数据表明，在某些霍奇金淋巴瘤（HL）和非霍奇金淋巴瘤（NHL）亚型中，由于编码它们的基因座的遗传扩增，PD-1 配体过度表达。淋巴瘤中 PD-L1 过度表达的其他机制也已经阐明。PD-1 阻断的早期临床试验报告显示，HL 中有显著疗效，而且对一些 NHL 也有活性。我们回顾了淋巴瘤中 PD-L1 表达的机制，以及该疾病中抗 PD-1 治疗的早期结果。
