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Neuroblastoma cells inhibit the immunostimulatory function of dendritic cells. J Pediatr Surg 2003 Jun;38(6):901-5

Date

06/05/2003

Pubmed ID

12778389

DOI

10.1016/s0022-3468(03)00119-2

Scopus ID

2-s2.0-0038657982   8 Citations

Abstract

PURPOSE: 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.

Author List

Chen X, Doffek K, Sugg SL, Shilyansky J

Author

Xiao Chen MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antigen Presentation
Antigens, CD
Apoptosis
B7-2 Antigen
Cell Communication
Cell Culture Techniques
Cells, Cultured
Dendritic Cells
Flow Cytometry
Humans
Immunophenotyping
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Membrane Glycoproteins
Neuroblastoma
T-Lymphocytes
Tumor Cells, Cultured
Tumor Escape
Tumor Necrosis Factor-alpha
Up-Regulation