Harnessing the expression of interleukin-15 and CD56 in immunotherapeutic strategies combating leukemia: a functional and mechanistic characterization

The "Breakthrough of the Year" of 2013, awarded by Science, was the burgeoning field of cancer immunotherapy. In spite of some great results, the search continues towards an ideal functioning of our immune cells, leaving a paramount question unanswered: can we identify specific cellular attributes denoting optimal activation and immune performance in combating cancer? In this project we will investigate the interleukin (IL)-15-mediated activation of immune cells, more specifically dendritic cells (DCs) and gd T cells, and their expression of CD56 in a model of acute myeloid leukemia. First, IL-2 and IL-15 will be compared for their immunostimulatory effect on gd T cells, conceivably strengthening the use of IL-15 in, among other, adoptive immunotherapy protocols. Induction of activation and enhancement of effector functions of gd T cells by these cytokines will be correlated with their CD56 expression. Next, we will delineate the cross-talk between our CD56+ and IL-15 expressing IL-15 DCs and gd T cells. Furthermore, the role of CD56 on these immune cells will be unraveled. This will give us the opportunity to finally answer the question whether CD56 expression is being indicative of an activated state, whether it actively leads to tumor cell killing and whether or not homodimeric interactions do play a role. Finally, mechanistic insight will be gained into the individual contribution of the IL-15 signaling pathways in induction of CD56 expression and immune cell activation.

Keywords:LEUKEMIA

Disciplines:Systems biology, Hematology, Immunology, Laboratory medicine