ASH Clinical News December 2014 | Page 61

Can the body’s own Natural Killer Cells be activated to target myeloma cells? Exploring the potential of the SLAMF7, KIR, and CD137 pathways SLAMF7 Natural Killer Cell SLAMF7 SLAMF7 Myeloma cell KIR Natural Killer Cell KIR Myeloma cell Ligand CD137 Natural Killer Cell CD137 Myeloma cell Ligand Signaling Lymphocytic Activation Molecule Family member 7 is a cell surface protein that is highly expressed on the surface of myeloma cells across disease stages and cytogenetic subtypes.21 SLAMF7 is also expressed on Natural Killer Cells, plasma cells, and other immune cells.21 The potential of the SLAMF7 pathway to regulate Natural Killer Cell cytotoxicity in multiple myeloma is currently under investigation. Killer cell Immunoglobulin-like Receptors are expressed on the surface of various immune cells, including Natural Killer Cells, and are key regulators of their activation.16 Myeloma cells are able to evade Natural Killer Cellmediated recognition and cytotoxicity by upregulating the ligand for inhibitory KIRs.5 The potential of the KIR pathway to regulate Natural Killer Cell activation in multiple myeloma is currently being studied. CD137 is a cell surface protein that can be upregulated on the surface of Natural Killer Cells, T cells and other immune cells, and its ligand is highly expressed on myeloma cells.17,22 The potential of the CD137 pathway to regulate Natural Killer Cell cytotoxicity in multiple myeloma is also being explored.