Jeong Ah-Reum, Ball Edward D, Goodman Aaron Michael
Division of Hematology and Oncology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Clin Med Insights Oncol. 2020 Dec 28;14:1179554920976366. doi: 10.1177/1179554920976366. eCollection 2020.
Treatment of cancer has transformed with the introduction of checkpoint inhibitors. However, the majority of solid tumor patients do not respond to checkpoint blockade. In contrast, the response rate to programmed cell death 1 (PD-1) blockade in relapsed/refractory classical Hodgkin lymphoma (cHL) is 65% to 84% which is the highest among all cancers. Currently, checkpoint inhibitors are only approved for cHL and primary mediastinal B-cell lymphoma as the responses to single-agent checkpoint blockade in other hematologic malignancies is disappointingly low. Various established biomarkers such as programmed cell death 1 ligand 1 (PD-L1) protein surface expression, mismatch repair (MMR) status, and tumor mutational burden (TMB) are routinely used in clinical decision-making in solid tumors. In this review, we will explore these biomarkers in the context of hematologic malignancies. We review characteristic 9p24.1 structural alteration in cHL and primary mediastinal B-cell lymphoma (PMBCL) as a basis for response to PD-1 inhibition, as well as the role of antigen presentation pathways. We also explore the reported frequencies of MMR deficiency in various hematologic malignancies and investigate TMB as a predictive marker.
随着检查点抑制剂的引入，癌症治疗发生了变革。然而，大多数实体瘤患者对检查点阻断无反应。相比之下，复发/难治性经典型霍奇金淋巴瘤（cHL）对程序性细胞死亡蛋白1（PD-1）阻断的反应率为65%至84%，这在所有癌症中是最高的。目前，检查点抑制剂仅被批准用于cHL和原发性纵隔B细胞淋巴瘤，因为在其他血液系统恶性肿瘤中，单药检查点阻断的反应率低得令人失望。各种已确立的生物标志物，如程序性细胞死亡蛋白1配体1（PD-L1）蛋白表面表达、错配修复（MMR）状态和肿瘤突变负荷（TMB），在实体瘤的临床决策中经常被使用。在本综述中，我们将在血液系统恶性肿瘤的背景下探讨这些生物标志物。我们回顾了cHL和原发性纵隔B细胞淋巴瘤（PMBCL）中特征性的9p24.1结构改变，作为对PD-1抑制反应的基础，以及抗原呈递途径的作用。我们还探讨了各种血液系统恶性肿瘤中报道的MMR缺陷频率，并研究了TMB作为一种预测标志物。
