Dendritic cell differentiation and IL-12 production in peripheral blood of pediatric solid tumor patients

Abstract

PURPOSE Monocyte-derived dendritic cells (DCs) show limited or inhibited maturation in the tumor microenvironment. We previously reported that soluble factors released from neuroblastoma (NB) cells inhibit the differentiation of monocytes obtained from healthy adults into mature DCs. We herein investigated the inhibitory effect of NB-derived soluble factors on the maturation of monocytes obtained from children with malignant tumors towards DCs. METHODS Blood samples were collected from 25 children with untreated malignant solid tumors and 30 children with non-neoplastic diseases (control group). Purified monocytes were cultured with GM-CSF/IL-4 and matured into DCs. DCs were cultured with supernatants of NB cell lines and evaluated for maturation by FACS and IL-12 production. RESULTS Maturation toward DCs and IL-12 production were similarly observed in the malignant tumor group and the control group. DC maturation and IL-12 production were significantly suppressed in both groups when cultured with NB culture supernatant. CONCLUSION Monocytes obtained from children with malignant tumors were capable of maturing into DCs, which functioned similarly to those from control cases. NB-derived soluble factors inhibited the DC maturation and the function of DCs equally, regardless of the patient's tumor burden. Our results suggest the non-specific and universal immunoinhibitory effect of NB-derived soluble factors.