Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1+ tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell non-Hodgkin lymphomas, including follicular lymphoma, which often displays abundant PD-1 expression on intratumoral T cells, and diffuse large B-cell lymphoma, which variably expresses PD-1 and PD-L1. In primary mediastinal large B-cell lymphoma, which frequently has 9p24.1 alterations, the ORR was 35% in a phase 2 trial of pembrolizumab. In contrast, the ORR with pembrolizumab was 0% in relapsed chronic lymphocytic leukemia (CLL) and 44% in CLL with Richter transformation in a phase 2 trial. T cells from CLL patients have elevated PD-1 expression; CLL PD-1+ T cells can exhibit a pseudo-exhaustion or a replicative senescence phenotype. PD-1 expression was also found in marginal zone lymphoma but not in mantle cell lymphoma, although currently anti-PD-1 clinical trial data are not available. Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas.

中文翻译：

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B细胞淋巴瘤中的PD-1表达和临床PD-1阻断

靶向 PD-1 免疫检查点的程序性细胞死亡蛋白 1 (PD-1) 阻断剂在治疗包括血液系统恶性肿瘤在内的晚期癌症方面表现出前所未有的临床疗效。本文回顾了 PD-1/程序性死亡配体 1 (PD-L1) 表达的前景以及当前在 B 细胞淋巴瘤中的 PD-1 阻断免疫治疗试验。最值得注意的是，在复发/难治性经典霍奇金淋巴瘤中，其经常增加 PD-1+ 肿瘤浸润 T 细胞、9p24.1 基因改变和高 PD-L1 表达，抗 PD-1 单药治疗已显示出显着的客观缓解率(ORR) 为 65% 至 87%，并在 1/2 期临床试验中获得持久的疾病控制。在一项 2 期试验中，缓解的中位持续时间为 16 个月。PD-1 阻断剂在 nivolumab 治疗复发/难治性 B 细胞非霍奇金淋巴瘤（包括滤泡性淋巴瘤）的 1 期试验中也显示出前景，滤泡性淋巴瘤通常在肿瘤内 T 细胞和弥漫性大 B 细胞上表现出丰富的 PD-1 表达淋巴瘤，其可变表达 PD-1 和 PD-L1。在经常有 9p24.1 改变的原发性纵隔大 B 细胞淋巴瘤中，在派姆单抗的 2 期试验中，ORR 为 35%。相比之下，在一项 2 期试验中，使用 pembrolizumab 的 ORR 在复发性慢性淋巴细胞白血病 (CLL) 中为 0%，在带有 Richter 转化的 CLL 中为 44%。CLL 患者的 T 细胞 PD-1 表达升高；CLL PD-1+ T 细胞可以表现出假衰竭或复制性衰老表型。在边缘区淋巴瘤中也发现了 PD-1 表达，但在套细胞淋巴瘤中没有发现，尽管目前尚无抗 PD-1 临床试验数据。在 B 细胞淋巴瘤的背景下讨论了 PD-1 阻断免疫治疗、治疗相关不良事件、超进展和联合治疗的机制和预测生物标志物。