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.
Curr Cancer Drug Targets. 2017;17(9):839-845. doi: 10.2174/1568009617666170906170348.
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.
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.
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.
Immunotherapies using anti-PD-1/PD-L1 strategies are a promising treatment options for patients with multiple myeloma.
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。
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。
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。
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。