Tumor's other immune targets: dendritic cells.
The induction of apoptosis in T cells is one of several mechanisms by which tumors escape immune recognition. We have investigated whether tumors induce apoptosis in dendritic cells (DC) by co-culture of murine or human DC with different tumor cell lines for 4-48 h. Analysis of DC morphological features, JAM assay, TUNEL, caspase-3-like and transglutaminase activity, Annexin V binding, and DNA fragmentation assays revealed a time- and dose-dependent induction of apoptosis in DC by tumor-derived factors. This finding is both effector and target specific. The mechanism of tumor-induced DC apoptosis involved regulation of Bcl-2 and Bax expression. Double staining of both murine and human tumor tissues confirmed that tumor-associated DC undergo apoptotic death in vivo. DC isolated from tumor tissue showed significantly higher levels of apoptosis as determined by TUNEL assay when compared with DC isolated from spleen. These findings demonstrate that tumors induce apoptosis in DC and suggest a new mechanism of tumor escape from immune recognition. DC protection from apoptosis will lead to improvement of DC-based immunotherapies for cancer and other immune diseases.
Esche
C
C
Biologic Therapeutics Program, University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA.
Lokshin
A
A
Shurin
G V
GV
Gastman
B R
BR
Rabinowich
H
H
Watkins
S C
SC
Lotze
M T
MT
Shurin
M R
MR
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D053938:DNA Fragmentation; D003713:Dendritic Cells / Q000276:immunology*; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D019253:Proto-Oncogene Proteins c-bcl-2; D014316:Tritium; D011503:Transglutaminases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases