Human dendritic cells mediate anti-tumor activity against hematopoietic tumor cells without direct contact and Fas/FasL killing pathway.
During maturation, the capacity of dendritic cells (DCs) to uptake and process antigens becomes diminished while the expression of MHC molecules and costimulatory molecules is up-regulated. These phenotypic changes make DCs potent antigen presenting cells with the ability to initiate and modulate immune responses. Recent findings have shown that DCs can mediate direct cytotoxicity toward tumor cells. Here, we investigated the effect of monocyte derived DC (moDC) on hematopoietic tumor cells by assessing the uptake of [methyl-3H]thymidine (3H-TdR), JAM test (radiometric assay for DNA fragmentation) and 51Cr-release assay. We found that moDCs significantly inhibited the growth of 6 tumor cell lines and stimulated another 4 cell lines independently of the expression of Fas protein. MoDCs also inhibited the proliferation of tumor cells in transwell culture, including two cell lines that were driven to proliferate by direct contact with moDCs. Apoptosis, but not cytolysis, was detected in all the cell lines inhibited by moDCs. In contrast, no cytostatic or cytotoxic effect was detected on K562 cells (chronic myeloid leukemia) and BY94 cells (sporadic Burkitt's lymphoma). The inhibitory activity of moDCs on Fas-expressing tumor cells fully persisted after the neutralization of FasL. Accordingly, there was no detection of FasL protein or FasL mRNA expression in moDC. These results suggest that moDCs can mediate a direct anti-tumor activity against hematopoietic tumor cells through cytostasis in absence of contact or through apoptosis without triggering the Fas/FasL pathway.
Ayres
Flávio Monteiro
FM
First Department of Internal Medicine, School of Medicine, Niigata University, Niigata 951-8510, Japan.
Narita
Miwako
M
Takahashi
Masuhiro
M
Yano
Toshio
T
Liu
Aichun
A
Toba
Ken
K
Furukawa
Tatsuo
T
Aizawa
Yoshifusa
Y
D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D053222:Fas Ligand Protein; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D019014:fas Receptor
C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor