Immune Functions of Signaling Lymphocytic Activation Molecule Family Molecules in Multiple Myeloma

Abstract

The signaling lymphocytic activation molecule (SLAM) family receptors are expressed on various immune cells and malignant plasma cells in multiple myeloma (MM) patients. In immune cells, most SLAM family molecules bind to themselves to transmit co-stimulatory signals through the recruiting adaptor proteins SLAM-associated protein (SAP) or Ewing’s sarcoma-associated transcript 2 (EAT-2), which target immunoreceptor tyrosine-based switch motifs in the cytoplasmic regions of the receptors. Notably, SLAMF2, SLAMF3, SLAMF6, and SLAMF7 are strongly and constitutively expressed on MM cells that do not express the adaptor proteins SAP and EAT-2. This review summarizes recent studies on the expression and biological functions of SLAM family receptors during the malignant progression of MM and the resulting preclinical and clinical research involving four SLAM family receptors. A better understanding of the relationship between SLAM family receptors and MM disease progression may lead to the development of novel immunotherapies for relapse prevention.

The numerous facets of 1q21+ in multiple myeloma: Pathogenesis, clinicopathological features, prognosis and clinical progress (Review)

“…Elotuzumab is a monoclonal antibody targeting signaling lymphocytic activation molecule family member 7 (SLAMF7), which is highly expressed by MM cells (139). Elotuzumab can not only directly act on SLAMF7 that is highly expressed on the surface of PCs to inhibit intercellular adhesion, thereby reducing the growth stimulation effect of stromal cells on myeloma cells, but also target, bind to and label SLAMF7 on the surface of myeloma cells, and enhance antibody-dependent cellular cytotoxicity in myeloma cells mediated by NK cells (140,141).…”

SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy

“…Additionally, SLAMF2, SLAMF8, and SLAMF9 lacks ITSM domains (Figure 1) (6). In immune cells that contain SLAM-family receptors containing ITSMs, SLAM/SAP and SLAM/EAT-2 complexes interact directly with Src family kinase Fyn and phospholipase Cg, respectively, and stimulate an activating signal within these immune cells (76). On the one hand, groundbreaking studies revealed that SLAM molecules acted as activating receptors in immune cells that expressed adaptors belonging to the SAP family.…”

Killer instincts: natural killer cells as multifactorial cancer immunotherapy

“…These SLAM-family receptors, excluding CD48 and SLAMF8, signal through ITSMs ( 247 ). SLAM-family receptors are homotypic, except for the partnership of 2B4 and CD48 ( 248 , 249 ).…”