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. 2018 Oct 5;9(78):34784-34793.
doi: 10.18632/oncotarget.26196.

Clinical Impact of Serum Soluble SLAMF7 in Multiple Myeloma

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Free PMC article

Clinical Impact of Serum Soluble SLAMF7 in Multiple Myeloma

Mariko Ishibashi et al. Oncotarget. .
Free PMC article

Abstract

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.

Keywords: CS1; SLAMF7; elotuzumab; multiple myeloma; soluble form.

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Circulating serum sSLAMF7 levels in MM patients according to disease stage
(A) Comparison of serum sSLAMF7 levels among healthy controls (Ctl., n=16) and patients with MGUS (n=16), asymptomatic MM (aMM, n=18), and symptomatic MM (sMM, n=85). Comparison of serum sSLAMF7 levels in MM patients according to the ISS (B) and R-ISS (C) stage (Table 1). The lower tables in each graph indicate the number of MM patients positive and negative for serum sSLAMF7.
Figure 2
Figure 2
Kaplan–Meier estimates of PFS (A) and OS (B) in MM patients positive (n=68) and negative for sSLAMF7 (n=31).
Figure 3
Figure 3. Levels of serum sSLAMF7 in MM patients before and after/during antimyeloma therapy
(A and B) MM patients who received antimyeloma therapy and achieved a complete response (CR) or partial response (PR). (C) An MM patient was treated with elotuzumab weekly for 2 cycles. BD, bortezomib-dexamethasone; Rd, lenalidomide-dexamethasone; VMP, bortezomib-melphalan-prednisone; PAD, bortezomib-doxorubicin-dexamethasone; VRD, bortezomib-lenalidomide-dexamethasone; sCR, stringent complete response; PD, progressive disease.
Figure 4
Figure 4. Inhibition of anti-SLAMF7-mediated ADCC activity against MM cells by rhSLAMF7
(A) Dose-dependent inhibition of anti-SLAMF7-mediated ADCC by rhSLAMF7. U266 cells treated with 20 μg/ml of anti-SLAMF7 antibody were co-cultured with NK-92MI cells at an effector : target ratio of 10:1. (B) In the ADCC assay, U266 cells treated with anti-SLAMF7 antibody were mixed with NK-92MI cells at different target : effector cell ratios. The data are expressed as mean ± SD of triplicate experiments. **P<0.01.

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