PMID- 11745422
OWN - NLM
STAT- MEDLINE
DCOM- 20020107
LR  - 20190708
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 94
IP  - 3
DP  - 2001 Nov 1
TI  - Immature dendritic cells kill ovarian carcinoma cells by a FAS/FASL pathway, 
      enabling them to sensitize tumor-specific CTLs.
PG  - 407-13
AB  - Dendritic cells (DCs) can acquire antigen(s) from apoptotic tumor cells, 
      resulting in an immunogen that can induce class I-restricted cytotoxic T 
      lymphocytes (CTLs) and protective tumor rejection. Here, we investigated whether 
      DCs derived from ascitic monocytes of patients with ovarian carcinoma could kill 
      autologous ovarian tumor cells and if as a result they would acquire antigen(s) 
      enabling them to induce a tumor-specific immunity. We found that the immature DCs 
      could exert a significant cytotoxicity towards autologous and allogeneic ovarian 
      tumor cells. This cytotoxicity was independent of Ca(2+) and could be inhibited 
      by anti-Fas IgG1 monoclonal antibody, indicating the involvement of the Fas/Fas 
      ligand (FasL) pathway in the cytotoxic mechanism. Further supporting this 
      conclusion, the ascitic monocyte-derived DCs expressed high levels of FasL mRNA 
      and intracellular FasL and significant levels of Fas were also revealed on the 
      surface of ovarian tumor cells. Coculture of DCs induced apoptosis in ovarian 
      carcinoma cells, as well as uptake of apoptotic tumor cells into the cytoplasma 
      of the DCs, as visualized by immunofluoresence. Autologous DCs cocultured with 
      apoptotic ovarian tumor cells were able to specifically stimulate tumor-specific 
      CTLs, whereas DCs cocultured with necrotic ovarian cells were unable to do so. 
      Collectively, these results demonstrate that immature DCs can kill autologous 
      ovarian carcinoma cells via the Ca(2+)-independent Fas/FasL pathway and that this 
      may have important consequences for their ability to stimulate tumor-specific 
      CTLs.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Yang, R
AU  - Yang R
AD  - Department of Oncology and Pathology, Karolinska Institutet, Karolinska Hospital, 
      Stockholm, Sweden. ryang@mail.jhmi.edu
FAU - Xu, D
AU  - Xu D
FAU - Zhang, A
AU  - Zhang A
FAU - Gruber, A
AU  - Gruber A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Antibodies, Monoclonal/metabolism
MH  - Apoptosis
MH  - Ascites/metabolism
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Calcium/metabolism
MH  - Cell Division
MH  - Coculture Techniques
MH  - Dendritic Cells/*metabolism
MH  - Fas Ligand Protein
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Jurkat Cells
MH  - Membrane Glycoproteins/biosynthesis/*metabolism
MH  - Microscopy, Fluorescence
MH  - Monocytes/metabolism
MH  - Ovarian Neoplasms/*metabolism
MH  - Phenotype
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Cytotoxic/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2001/12/18 10:00
MHDA- 2002/01/10 10:01
CRDT- 2001/12/18 10:00
PHST- 2001/12/18 10:00 [pubmed]
PHST- 2002/01/10 10:01 [medline]
PHST- 2001/12/18 10:00 [entrez]
AID - 10.1002/ijc.1484 [pii]
AID - 10.1002/ijc.1484 [doi]
PST - ppublish
SO  - Int J Cancer. 2001 Nov 1;94(3):407-13. doi: 10.1002/ijc.1484.