Neuroblastoma cells inhibit the immunostimulatory function of dendritic cells.
OBJECTIVE
Dendritic cells (DC) are critical for induction of antitumor immunity. Recent studies suggest that tumors may avoid immune destruction by inhibiting DC function. The authors investigated the effect of neuroblastoma (NB) on surface antigen expression and T cell activation by DCs.


METHODS
DCs were generated in the presence of granulocyte and macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) from peripheral blood of healthy donors. On day 6 of culture, DCs were exposed to human NB cells and were analyzed by flow cytometry.


RESULTS
The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) failed to upregulate the expression of HLA-DR and costimulatory molecule CD86 by DCs that were cultured with NB. Conversely, upregulation was preserved when DCs were cultured in the absence of NB. Exposure to NB also led to apoptosis of DCs as shown by 2-fold increase in surface phosphatidylserine. It appears that direct contact was required to inhibit DC maturation, because DCs separated from NB cells using a transwell insert did not suppress surface antigen expression. Finally, DCs exposed to NB inhibited the proliferation of allogeneic T cells in mixed lymphocyte reactions.


CONCLUSIONS
These findings have significant implications for tumor-pulsed DC vaccines in the treatment of NB and suggest a mechanism by which NB escape rejection.
Chen
Xiao
X
Children's Hospital of Wisconsin, Milwaukee, WI, USA.
Doffek
Kara
K
Sugg
Sonia L
SL
Shilyansky
Joel
J
D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000276:immunology; D051940:B7-2 Antigen; D002450:Cell Communication / Q000276:immunology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009447:Neuroblastoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha