SLAMF7 - SLAM family member 7 |Elisa - Clia - Antibody - Protein

Background

SLAMF7 (SLAM Family Member 7), also known as CS1 (CD2 subset 1) or CRACC (CD319), is a cell surface glycoprotein belonging to the Signaling Lymphocyte Activation Molecule (SLAM) family within the immunoglobulin superfamily. SLAMF7 is primarily expressed on the surface of immune cells, especially on natural killer (NK) cells, plasma cells, and certain T-cell subsets, as well as dendritic cells and monocytes. This receptor plays a key role in immune cell activation, adhesion, and signal transduction, significantly influencing immune responses.

SLAMF7 is particularly relevant in the context of immune surveillance and tumor cell recognition, as it acts as a co-stimulatory molecule for NK cells, enhancing their cytotoxic function against abnormal cells. In the tumor microenvironment, SLAMF7 can either promote anti-tumor immunity or, in some cases, contribute to immune evasion mechanisms that facilitate cancer cell survival. Its expression in multiple myeloma, where it is typically highly expressed, has made it a target for immunotherapy. The development of monoclonal antibodies against SLAMF7, like elotuzumab, has underscored its significance in cancer therapy.

Protein Structure

SLAMF7 is a type I transmembrane protein with a well-defined structure that facilitates its function in immune cell interactions and signaling:

Extracellular Domain:

• The extracellular domain of SLAMF7 consists of two immunoglobulin-like domains: a V-type domain and a C2-type domain. These domains allow SLAMF7 to interact with itself (homophilic interaction) as well as potentially with other proteins in the SLAM family.
• The immunoglobulin domains are critical for ligand binding and mediate SLAMF7's interactions on the surface of immune cells. This structural arrangement allows SLAMF7 to participate in cell adhesion and signaling events that regulate immune cell activation.

Transmembrane Domain:

• The transmembrane region anchors SLAMF7 into the cell membrane, stabilizing its position and orientation. This domain is essential for the proper localization of SLAMF7, ensuring that it is correctly situated to interact with other cell surface receptors or ligands.

Intracellular (Cytoplasmic) Domain:

• SLAMF7 has an intracellular tail that contains a motif similar to the Immunoreceptor Tyrosine-Based Switch Motif (ITSM), which plays a crucial role in signal transduction. This ITSM motif is a docking site for signaling molecules and allows SLAMF7 to recruit SLAM-associated protein (SAP) and other signaling adaptors.
• Through the ITSM, SLAMF7 can activate pathways that influence cytotoxicity and cytokine release, specifically by engaging SAP and other downstream signaling partners. This activation is essential for SLAMF7’s role in immune cell regulation, allowing it to modulate the cytotoxic activity of NK cells and other immune functions.

Classification and Subtypes

SLAMF7 is part of the SLAM family of receptors, which includes other related proteins like SLAMF1, SLAMF2, and SLAMF3. These proteins are characterized by similar structural features, including the presence of immunoglobulin-like domains and ITSM motifs in their cytoplasmic tails. Although no direct subtypes of SLAMF7 exist, the entire SLAM family shares a conserved role in immune regulation through homophilic interactions and engagement with adaptor proteins like SAP. The SLAM receptors are widely studied for their involvement in both innate and adaptive immune responses, with SLAMF7 standing out for its significant role in modulating NK cell function.

Function and Biological Significance

SLAMF7 is involved in various immune cell processes, particularly in enhancing immune cell-mediated cytotoxicity and cytokine production:

Regulation of NK Cell Activity:

• SLAMF7 functions as a co-activating receptor on NK cells, enhancing their cytotoxic response against malignant or infected cells. The homophilic binding between SLAMF7 molecules on adjacent cells (e.g., NK cells and target cells) triggers signals that enhance NK cell activation.
• The interaction with SAP following ITSM motif engagement further promotes the cytotoxic function of NK cells by facilitating immune synapse formation, which is essential for targeted cell killing.

Role in Plasma Cells and Myeloma:

• SLAMF7 is highly expressed in plasma cells and is particularly abundant in multiple myeloma cells, a cancer of plasma cells. SLAMF7 promotes the survival and proliferation of these cells, partly by engaging in cell-cell adhesion interactions that help the cells evade immune surveillance.
• Its expression on multiple myeloma cells has led to the development of targeted immunotherapies, aiming to enhance immune recognition and destruction of these malignant cells.

Signal Transduction and Immune Modulation:

• SLAMF7’s intracellular ITSM motif recruits SAP and related signaling molecules, which leads to the activation of downstream signaling pathways that mediate immune responses. This signaling can promote the production of cytokines like interferon-gamma (IFN-γ), further activating immune cells and reinforcing the anti-tumor response.
• Besides NK cells, SLAMF7 can influence other immune cell types, including T cells and dendritic cells, modulating their activity and promoting overall immune activation. This function is particularly relevant in the context of infections and cancer, where a coordinated immune response is essential.

Modulation of Immune Surveillance in Cancer:

• SLAMF7 plays a dual role in cancer. On one hand, it can stimulate NK cell activity against tumor cells; on the other hand, it is often highly expressed on the surface of multiple myeloma cells, where it contributes to immune evasion. By enhancing the adherence and clustering of myeloma cells, SLAMF7 can promote cell survival and reduce susceptibility to NK cell-mediated cytotoxicity.

Clinical Issues

SLAMF7’s involvement in immune cell regulation has made it a focus of clinical research, particularly in cancer immunotherapy:

Therapeutic Target in Multiple Myeloma:

• SLAMF7 is a therapeutic target in multiple myeloma due to its high expression on myeloma cells. The monoclonal antibody elotuzumab targets SLAMF7, binding to it on the surface of myeloma cells and marking them for destruction by NK cells. This antibody works synergistically with other immune-modulating agents, enhancing the immune response against myeloma cells.
• Elotuzumab’s use in combination therapies has been shown to improve survival rates in multiple myeloma patients, highlighting SLAMF7’s potential as a therapeutic target. The antibody promotes NK cell activation and directs the immune response specifically toward malignant plasma cells.

Potential Implications in Autoimmune Disorders:

• Given its role in immune modulation, SLAMF7’s dysregulation may contribute to immune-related diseases. Abnormal expression or function of SLAMF7 could theoretically alter immune cell activation patterns, potentially playing a role in autoimmune disorders, although more research is needed in this area.

Role in Infectious Disease:

• SLAMF7’s influence on immune cell function suggests it could play a role in the response to infectious diseases. Enhanced expression of SLAMF7 may promote immune responses to clear pathogens, but its exact role in infection control and whether it could serve as a target in infectious disease therapies are areas of ongoing research.

Summary

SLAMF7, a type I transmembrane glycoprotein in the SLAM family, is crucial for regulating immune cell activation, particularly in NK cells and plasma cells. Structurally, SLAMF7 features extracellular immunoglobulin-like domains that facilitate interactions with other immune cells, a transmembrane domain for membrane localization, and an intracellular ITSM motif critical for signal transduction. Through its signaling capabilities, SLAMF7 enhances NK cell cytotoxicity and plays a role in immune surveillance against tumors and infected cells.

SLAMF7’s overexpression in multiple myeloma has spurred the development of targeted therapies, with elotuzumab marking a breakthrough in immunotherapy by exploiting SLAMF7 to direct NK cells against malignant cells. While SLAMF7’s primary significance lies in cancer immunotherapy, it has broader implications for immune modulation, with potential roles in infectious diseases and autoimmune conditions. Overall, SLAMF7 is an important immune regulatory molecule with a promising therapeutic potential due to its unique role in immune cell signaling and tumor recognition.