Effect of the Antigenic Differences of Neuroblastoma on the Maturation and Immunoactivity in Dendritic Cells

Abstract

Purpose: Most of neuroblastoma (NB) patients present with advanced disease, and the survival of patients with advanced stage disease remains poor, despite of aggressive therapy such as high dose chemotherapy and autologouse stem cell transplantation. It is necessary to control of minimal residual disease in NB patients in order to reduce relapse rate. Dendritic cells (DC) are crucial for induction of antitumor immunity. Recent studies suggest that tumors avoid immune surveillence by inhibiting DC function. We investigated the effect of NB cells about maturation and/or function of dendritic cells using peripheral blood monocytes as dendritic cell source. Methods: DCs were generated in the presence of GM-CSF (granulocyte and marcrophage colony-stimulating factor) and IL (interleukin)-4 from peripheral blood of healthy donors. DCs were exposed to human some kinds of NB cells or NB lysate. And the maturation of DC was induced by adding TNF (tumor necrosis factor)-α, IL-1β, IL-6 and prostaglandin E2 for 2 days. DCs were analyzed by flow cytometry and mixed lymphocyte reactions. Results: DCs exposed to NB cells didn´t upregulate the expression of CD83, HLA-DR, CD80 and CD86, and DCs exposed to NB lysate didn´t upregulate the expression of CD83 and HLA-DR. DCs exposed to NB cells and NB lysate inhibited the proliferation of allogenic T cells in mixed lymphocyte reactions. Conclusion: NB cells induced impaired maturation and immune function of DCs. These findings have significant implications for DC-based immunotherapy in the treatment NB and suggested that it was necessary to develop a new method of priming antigen to dendritic cells at NB immunotherapy.