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理解弥漫性大 B 细胞淋巴瘤中 PD-1/PD-L1 通路相关的免疫逃逸和治疗靶点。

Understanding Immune Evasion and Therapeutic Targeting Associated with PD-1/PD-L1 Pathway in Diffuse Large B-cell Lymphoma.

机构信息

Department of Hematology-Oncology, Hanyang University Hanmaeum Changwon Hospital, 51497 Changwon, Korea.

Division of Hematology-Oncology, Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Seoul Hospital, 04763 Seoul, Korea.

出版信息

Int J Mol Sci. 2019 Mar 15;20(6):1326. doi: 10.3390/ijms20061326.

Abstract

In tumor microenvironment, the programmed death 1 (PD-1) immune checkpoint has a crucial role of mechanism of T cell exhaustion leading to tumor evasion. Ligands of PD-1, programmed death ligand 1/2 (PD-L1/L2) are over-expressed in tumor cells and participate in prolonged tumor progression and survivals. Recently, clinical trials for patients who failed to obtain an optimal response prior to standardized chemotherapy in several solid cancers have been focused on targeting therapy against PD-1 to reduce disease progression rates and prolonged survivals. Since various inhibitors targeting the immune checkpoint in PD-1/PD-L1 pathway in solid cancers have been introduced, promising approach using anti-PD-1 antibodies were attempted in several types of hematologic malignances. In diffuse large B cell lymphoma (DLBCL) as the most common and aggressive B cell type of non-Hodgkin's lymphoma, anti-PD-1 and anti-PD-L1 antibodies were studies in various clinical trials. In this review, we summarized the results of several studies associated with PD-1/PD-L1 pathway as an immune evasion mechanism and described clinical trials about targeting therapy against PD-1/PD-L1 pathway in DLBCL.

摘要

在肿瘤微环境中,程序性死亡 1 (PD-1) 免疫检查点在 T 细胞耗竭导致肿瘤逃逸的机制中起着关键作用。PD-1 的配体,程序性死亡配体 1/2 (PD-L1/L2) 在肿瘤细胞中过度表达,并参与肿瘤的长期进展和存活。最近,针对几种实体瘤中在标准化化疗前未能获得最佳反应的患者的临床试验集中在针对 PD-1 的靶向治疗上,以降低疾病进展率并延长存活期。由于已经引入了针对 PD-1/PD-L1 通路中免疫检查点的各种抑制剂,因此在几种血液恶性肿瘤中尝试了使用抗 PD-1 抗体的有前途的方法。在弥漫性大 B 细胞淋巴瘤 (DLBCL) 中,作为最常见和侵袭性的非霍奇金淋巴瘤 B 细胞类型,在各种临床试验中研究了抗 PD-1 和抗 PD-L1 抗体。在这篇综述中,我们总结了与 PD-1/PD-L1 通路作为免疫逃逸机制相关的几项研究的结果,并描述了针对 DLBCL 中 PD-1/PD-L1 通路的靶向治疗的临床试验。

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