Clinical impact of serum soluble SLAMF7 in multiple myeloma.
Clinical impact of serum soluble SLAMF7 in multiple myeloma.
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DOI：
10.18632/oncotarget.26196
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发表时间：
2018-10-05
期刊：
影响因子：
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通讯作者：
Tamura, Hideto
中科院分区：
文献类型：
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作者：
Ishibashi, Mariko;Soeda, Saori;Tamura, Hideto
信号传导淋巴细胞活化分子家族（SLAMF 7;也称为CS 1或CD 319）在来自多发性骨髓瘤（MM）的浆细胞以及自然杀伤（NK）细胞上高度表达，并且是埃罗妥珠单抗的众所周知的治疗靶标。本研究的目的是评价MM患者（n=103）血清可溶性SLAMF 7（sSLAMF 7）水平的临床意义以及sSLMF 7对抗SLAMF 7抗体的抗肿瘤活性的影响。31%的MM患者，但不是单克隆丙种球蛋白病患者和健康对照，血清sSLAMF 7的可检测水平，这在晚期MM患者中显著增加。此外，与sSLAMF 7阴性患者相比，sSLAMF 7阳性患者的MM表现出侵袭性临床特征，无进展生存期较短。在MM治疗的应答者中，与治疗前相比，sSLAMF 7水平检测不到或降低。此外，抗SLAMF 7抗体介导的NK细胞对MM细胞系的抗体依赖性细胞毒性被重组SLAMF 7蛋白抑制。因此，我们的研究结果表明，高浓度的sSLAMF 7，其可以短暂抑制埃罗妥珠单抗的治疗效果，可能是MM患者疾病进展的有用指标。
The signaling lymphocytic activation molecule family (SLAMF7; also known as CS1 or CD319) is highly expressed on plasma cells from multiple myeloma (MM) as well as natural killer (NK) cells and is a well-known therapeutic target of elotuzumab. The objective of this study was to evaluate the clinical significance of serum soluble SLAMF7 (sSLAMF7) levels in patients with MM (n=103) and furthermore the impact of sSLMF7 on the antitumor activity of anti-SLAMF7 antibody. Thirty-one percent of MM patients, but not patients with monoclonal gammopathy of undetermined significance and healthy controls, had detectable levels of serum sSLAMF7, which were significantly increased in advanced MM patients. Further, MM in sSLAMF7-postive patients exhibited aggressive clinical characteristics with shorter progression-free survival times in comparison with sSLAMF7-negative patients. In responders to MM therapy, the levels of sSLAMF7 were undetectable or decreased compared with those before treatment. In addition, the anti-SLAMF7 antibody-mediated antibody-dependent cellular cytotoxicity of NK cells against MM cell lines was inhibited by recombinant SLAMF7 protein. Thus, our findings suggest that high concentrations of sSLAMF7, which could transiently suppress the therapeutic effects of elotuzumab, may be a useful indicator of disease progression in MM patients.