Impaired Actin Polymerization Results in Defective Immunological Synapse Formation in T Cells in Chronic Lymphocytic Leukemia

Cancer is associated with immune deficiency, but the molecular basis for this is poorly defined. We have previously demonstrated that multiple gene expression abnormalities are induced in patients with chronic lymphocytic leukemia (CLL) including defects within the actin cytoskeleton formation pathways. Based on this data, we hypothesized that failure of actin polymerization would result in defects in the formation of the immunological synapse (IS) which is critical for T cell activation and effector function. To assess this, actin polymerization at the IS in T cells in response to superantigen-pulsed B cells (APCs) was visualized using confocal microscopy. We observed significantly reduced ability to polymerize actin at the IS (> 50% reduction) in autologous CD4 and CD8 T cells from previously untreated CLL patients compared to age-matched healthy donors (p