摘要
背景:多发性骨髓瘤患者患有免疫系统失调,针对免疫系统(例如单克隆抗体或特异性细胞治疗如CAR-T细胞)的新治疗方案进入临床实践,但是耗尽的免疫系统阻碍了更有效的免疫治疗。针对微环境中的免疫功能障碍可能是免疫介导治疗的潜在靶标。 方法:在这里,我们回顾当前关于在耗尽的T和B细胞表面表达的程序性死亡1(PD-1)受体的文献和知识,其配体PD-L1在骨髓瘤细胞上表达并抑制T细胞介导细胞凋亡。 结果:程序性死亡1(PD-1)受体在耗尽的T和B细胞表面表达,其配体PD-L1在骨髓瘤细胞上表达并抑制T细胞介导的细胞凋亡。近来,通过单克隆抗体抑制这种“检查点”已经显示在实体瘤和恶性淋巴瘤中的高活性。在多发性骨髓瘤患者中,PD-L1在骨髓瘤细胞上过表达,PD1在T细胞上表达,表明PD-1 / PD-L1在免疫抑制微环境中起主要作用。 结论:使用抗PD-1 / PD-L1策略的免疫治疗是多发性骨髓瘤患者的有希望的治疗方案。
关键词: Coinhibitory分子PD-1,微环境,多发性骨髓瘤,T细胞介导的凋亡,PD-L1,免疫抑制。
图形摘要
Current Cancer Drug Targets
Title:Coinhibitory Molecule PD-1 as a Therapeutic Target in the Microenvironment of Multiple Myeloma
Volume: 17 Issue: 9
关键词: Coinhibitory分子PD-1,微环境,多发性骨髓瘤,T细胞介导的凋亡,PD-L1,免疫抑制。
摘要: Background: Patients with Multiple Myeloma suffer from dysregulation of the immune system and new therapeutic options targeting the immune systems such as monoclonal antibodies or specific Cell therapy such as CAR-T cells have entered clinical practice, but the exhausted immune system hampered a more effective immunotherapy. Targeting the immunological dysfunction in the microenviroment might be a potential target for immune-mediated therapies.
Method: Here we review the current literature and knowledge about the programmed death 1 (PD-1) receptor which is expressed on the surface of exhausted T and B cells and its ligand PD-L1 is expressed on myeloma cells and inhibits T cell-mediated apoptosis.
Results: The programmed death 1 (PD-1) receptor is expressed on the surface of exhausted T and B cells and its ligand PD-L1 is expressed on myeloma cells and inhibits Tcell-mediated apoptosis. Inhibiting such “checkpoint” by monoclonal antibodies recently has been shown high activity in solid tumors and malignant lymphomas. In patients with multiple myelomaPD-L1 is overexpressed on myeloma cells and PD1 on T-cells suggesting an active role of PD-1/PD-L1 in the immunosuppressive microenvironment.
Conclusion: Immunotherapies using anti-PD-1/PD-L1 strategies are a promising treatment options for patients with multiple myeloma.
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Cite this article as:
Coinhibitory Molecule PD-1 as a Therapeutic Target in the Microenvironment of Multiple Myeloma, Current Cancer Drug Targets 2017; 17 (9) . https://dx.doi.org/10.2174/1568009617666170906170348
DOI https://dx.doi.org/10.2174/1568009617666170906170348 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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