Induction of suppressive phenotype in monocyte-derived dendritic cells by leukemic cell products and IL-1β

Professional antigen-presenting cells, dendritic cells (DCs) play an important role in controlling tumors. It is known that solid tumor cell products inhibit DC differentiation. Recently a similar effect produced by leukemic cell products has been demonstrated. In this case, leukemic cell products induced the secretion of IL-1β by monocytes undergoing differentiation. The aim of the present work was to characterize and to compare the development of monocyte-derived DCs under the influence of leukemic cell products (K562 supernatant) or exogenous IL-1β. It became clear that leukemic cell products and IL-1β differentially modulate some of the parameters studied on monocytes stimulated to differentiate into DCs. In the presence of K562 supernatant, the expression of the macrophage markers CD16 and CD68 were higher than in immature DCs control. Contrasting with IL-1β, leukemic cell products possibly favor the development of cells with macrophage markers. In addition, CD80 and CD83 expressions were also higher in the presence of tumor supernatant whereas HLA-DR was lower. In the presence of IL-1β, only CD80 was increased. Furthermore, it was observed that when monocytes were induced to differentiate into DCs in the presence of tumor supernatant and then activated, they expressed less CD80 and CD83 than activated DCs control. A reduced expression of CD83 following activation was also seen in cells differentiated with IL-1β. TGF-β and VEGF were found in the tumor supernatants. Moreover, the exposure to tumor supernatant or IL-1β stimulated IL-10 production while decreased IL-12 production by activated DCs. Finally, these results suggest that the addition of products released by leukemic cells or, more discreetly, the addition of IL-1β affects DC differentiation, inducing a suppressive phenotype.