Hypersialylation protects Myeloma cells from NK cell mediated killing and this can be overcome by targeted desialylation using a sialyltransferase inhibitor.

Abstract

Evading Natural Killer (NK) cell-mediated immunosurveillance is key to the survival of Multiple Myeloma (MM) cells. Recently, attention has focused to the role of the hypersialylation in facilitating immune-evasion of NK cells. Abnormal cell surface sialylation is considered a hallmark of cancer, with growing evidence implicating hypersialylation in disease progression in MM. Certain sialylated glycans can act as ligands for the sialic acid-binding immunoglobulin-like lectin (Siglec) receptors expressed by NK cells (Siglec-7 and Siglec-9). These ITIM motif-containing inhibitory receptors are similar to PD-1, transmitting an inhibitory signal upon sialic acid engagement. We hypothesized that desialylation of MM cells or targeted interruption of Siglec expression could lead to enhanced NK cell killing of MM cells.