The signaling lymphocytic activation molecule (SLAM) receptor family (SLAMF) consists of nine glycoproteins that belong to the CD2 superfamily of immunoglobulin (Ig) domain-containing molecules. SLAMF receptors modulate the differentiation and activation of a wide range of immune cells. Individual SLAMF receptors are expressed on the surface of hematopoietic stem cells, hematopoietic progenitor cells, B cells, T cells, NK cells, NKT cells, monocytes, macrophages, dendritic cells, neutrophils, and platelets. The expression of SLAMF receptors was studied during normal B cell maturation. Several SLAMF receptors were also detected in cancer cell lines of B-lymphoid origin and in pathological B cells from patients with B cell chronic lymphoproliferative disorders (B-CLPD), the most frequent hematological malignancies in adults. This review summarizes current knowledge on the expression of SLAMF receptors and their adaptor proteins SAP and EAT-2 in B-CLPD. Several SLAMF receptors could be regarded as potential diagnostic and differential diagnostic markers, prognostic factors, and targets for the development of novel drugs for patients with B-CLPD.

SLAMF7, also known as CD319, a SLAM (signaling lymphocytic activation molecule) family receptor, is relatively weakly expressed on chronic lymphocytic leukemia (CLL) B cells. This study evaluated the ability of elotuzumab (E), an anti-SLAMF7/CD319 antibody, to induce antibody-dependent cellular cytotoxicity (ADCC) against CLL cell lines (MEC-1, MEC-2, CI, HG-3, PGA-1, WA-OSEL). ADCC was assessed by flow cytometry using E (100 μg/mL), rituximab (R, 100 μg/mL), and their combination (E + R). CLL lines served as targets (T), while peripheral blood mononuclear cells (PBMCs) or NK cells from healthy donors served as effectors (E) at an 8:1 E:T ratio for 4 h. With PBMCs, E-induced ADCC ranged from 1.3 ± 1.2% (PGA-1) to 14.6 ± 8.1% (MEC-1); R-induced ADCC ranged from 9.2 ± 4.6% (PGA-1) to 16.6 ± 9.4% (WA-OSEL). With NK cells, E-induced ADCC ranged from 1.8 ± 3.7% (PGA-1) to 27.3 ± 4.7% (MEC-1); R-induced ADCC ranged from 5.1 ± 4.3% (PGA-1) to 27.5 ± 13.6% (CI). E outperformed R in MEC-1, while R was superior elsewhere. Cell lines with higher SLAMF7/CD319 expression displayed increased sensitivity to E. Cell lines with del17p showed higher SLAMF7/CD319 expression. The combination of E + R showed no significant synergy over monotherapies. In conclusion, elotuzumab induced significant ADCC in CLL cells, warranting further therapeutic evaluation.