Clinical impact of serum soluble SLAMF7 in multiple myeloma
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Mariko Ishibashi1,2, Saori Soeda1, Makoto Sasaki3, Hiroshi Handa4, Yoichi Imai5, Norina Tanaka6, Sakae Tanosaki7, Shigeki Ito8, Takeshi Odajima9, Hiroki Sugimori10, Toshio Asayama1, Mika Sunakawa1, Yuta Kaito1, Ryosuke Kinoshita1, Yasuko Kuribayashi1, Asaka Onodera1, Keiichi Moriya1, Junji Tanaka6, Yutaka Tsukune3, Norio Komatsu3, Koiti Inokuchi1 and Hideto Tamura1
1Department of Hematology, Nippon Medical School, Tokyo, Japan
2Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan
3Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan
4Department of Hematology, Gunma University, Gunma, Japan
5Department of Hematology and Oncology, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
6Department of Hematology, Tokyo Women’s Medical University, Tokyo, Japan
7Department of Hematology, The Fraternity Memorial Hospital, Tokyo, Japan
8Department of Clinical Oncology, Iwate Medical University School of Medicine, Iwate, Japan
9Faculty of Health Science, Daito Bunka University Graduate School of Sports and Health Science, Tokyo, Japan
10Department of Preventive Medicine, Daito Bunka University Graduate School of Sports and Health Science, Saitama, Japan
Hideto Tamura, email: [email protected]
Keywords: multiple myeloma; SLAMF7; soluble form; CS1; elotuzumab
Received: May 17, 2018 Accepted: September 17, 2018 Published: October 05, 2018
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.
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