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抑制性分子 PD-1 作为多发性骨髓瘤微环境中的治疗靶点。

Coinhibitory Molecule PD-1 as a Therapeutic Target in the Microenvironment of Multiple Myeloma.

机构信息

Multiple Myeloma Program, Division of Hematology and Hematologic Malignancies, University of Utah, Huntsman Cancer Institute, Salt Lake City, UTAH. United States.

Department of Stem Cell Transplantatio, University Medical Center Hamburg-Eppendorf, Martinistrabe 52, 20246 Hamburg. Germany.

出版信息

Curr Cancer Drug Targets. 2017;17(9):839-845. doi: 10.2174/1568009617666170906170348.

Abstract

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.

摘要

背景

多发性骨髓瘤患者的免疫系统失调,针对免疫系统的新治疗选择,如单克隆抗体或特定的细胞疗法,如 CAR-T 细胞,已经进入临床实践,但衰竭的免疫系统阻碍了更有效的免疫疗法。针对微环境中的免疫功能障碍可能是免疫介导治疗的一个潜在目标。

方法

在这里,我们回顾了目前关于程序性死亡 1(PD-1)受体的文献和知识,该受体表达在衰竭的 T 和 B 细胞表面,其配体 PD-L1 表达在骨髓瘤细胞上,并抑制 T 细胞介导的细胞凋亡。

结果

程序性死亡 1(PD-1)受体表达在衰竭的 T 和 B 细胞表面,其配体 PD-L1 表达在骨髓瘤细胞上,并抑制 T 细胞介导的细胞凋亡。最近,通过单克隆抗体抑制这种“检查点”在实体瘤和恶性淋巴瘤中显示出了很高的活性。在多发性骨髓瘤患者中,骨髓瘤细胞上过度表达 PD-L1,T 细胞上表达 PD1,提示 PD-1/PD-L1 在免疫抑制微环境中发挥积极作用。

结论

使用抗 PD-1/PD-L1 策略的免疫疗法是多发性骨髓瘤患者有前途的治疗选择。

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