LAUSR

Targeting Januskinase (JAK) has revolutionized the treatment of myeloproliferative neoplasms. The JAK inhibitor ruxolitinib improved the outcome and quality of life of patients dramatically at the cost of increased risk of infections. As previously shown, ruxolitinib severly impairs the differentiation of peripheral blood mononuclear cells to monocyte derived dendritic cells and inhibits the function of dendritic cells in vitro and in vivo, which expanded its use as immunomodulatory compound. Pacritinib is a novel JAK inhibitor which will soon be approved for the treatment of myeloproliferative neoplasms and has shown first promising results. Here, we investigate the impact of the novel JAK inhibitor pacritinib on the function of monocyte derived dendritic cells and compared it to ruxolitinib. Pacritinib, in contrast to ruxolitinib exhibits only mild suppressive effects on dendritic cells. The upregulation of activation markers and CCR7 after TLR4-ligation is not or only marginally affected by pacritinib. Pacritinib, applied in concentrations reflecting patient´s plasma levels, reduces IL-12 secretion, whereas IL-6 and TNFα levels are unchanged at this concentration. In conclusion, the immunosuppressive effect of pacritinib on dendritic cells is significantly less pronounced than the effect ruxolitinib. Therefore, our data may help to identify those patients with myelofibrosis who may benefit from pacritinib treatment.