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PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

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单位: [1]Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA; [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Hematol, Wuhan, Hubei, Peoples R China; [3]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Canc Biol Res Ctr, Wuhan, Hubei, Peoples R China; [4]Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA
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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.

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基金编号: R01CA138688 R01CA187415 1RC1CA146299 P50CA136411 P50CA142509 CA016672 81230052 81630006 R01CA138688 P50CA136411 P30CA016672 P50CA142509 RC1CA146299 R01CA187415

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出版当年[2017]版:
大类 | 1 区 医学
小类 | 1 区 血液学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 血液学
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出版当年[2016]版:
Q1 HEMATOLOGY
最新[2023]版:
Q1 HEMATOLOGY

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第一作者单位: [1]Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA;
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通讯机构: [1]Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA; [4]Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA
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