Pianko Matthew J, Liu Yuzhou, Bagchi Srishti, Lesokhin Alexander M
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Mount Sinai St. Luke's and Mount Sinai West, New York, NY, USA.
Stem Cell Investig. 2017 Apr 19;4:32. doi: 10.21037/sci.2017.03.04. eCollection 2017.
Immune checkpoint blockade has revolutionized the treatment of cancer, with impressive responses seen in a broad variety of tumor types. Blockade of immune checkpoints and immune signaling antibodies has shown promise in multiple types of hematologic malignancies (HMs), with dramatic single agent responses for pembrolizumab and nivolumab in Hodgkin lymphoma (HL). In this review, we outline the current state of immune checkpoint blockade drug development in HMs, and discuss mechanisms of activity and resistance, and highlight potential targets in the immune tumor microenvironment (TME). Blockade of T-cell checkpoint molecules PD-1/PD-L1 and CTLA-4 are the most clinically mature of the immune checkpoint strategies. Novel and upcoming strategies for immune checkpoint blockade drug development in HMs using innovative combinations to modulate immunologic targets shows significant promise as a way to expand the number of patients with blood cancers who could benefit from immunotherapy.
免疫检查点阻断彻底改变了癌症治疗方式,在多种肿瘤类型中都观察到了令人瞩目的反应。免疫检查点阻断和免疫信号抗体在多种血液系统恶性肿瘤(HM)中显示出前景,派姆单抗和纳武单抗在霍奇金淋巴瘤(HL)中作为单药治疗产生了显著反应。在本综述中,我们概述了血液系统恶性肿瘤中免疫检查点阻断药物研发的现状,讨论了其作用机制和耐药机制,并强调了免疫肿瘤微环境(TME)中的潜在靶点。T细胞检查点分子PD-1/PD-L1和CTLA-4的阻断是免疫检查点策略中临床最成熟的。利用创新组合调节免疫靶点的血液系统恶性肿瘤免疫检查点阻断药物研发的新策略和即将出现的策略,作为一种扩大可从免疫治疗中获益的血癌患者数量的方法,显示出巨大前景。