PMID- 16000951
OWN - NLM
STAT- MEDLINE
DCOM- 20051017
LR  - 20221207
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 28
IP  - 4
DP  - 2005 Jul-Aug
TI  - Chemosensitization of pancreatic carcinoma cells to enhance T cell-mediated 
      cytotoxicity induced by tumor lysate-pulsed dendritic cells.
PG  - 332-42
AB  - Dendritic cells (DCs) can induce cytotoxic T-cell (CTL) responses against tumor 
      antigens in vitro and in vivo, yet few cancer patients experience tumor 
      regression after DC-based vaccination. Combination with other treatment 
      modalities, such as radiation or pharmacologic anticancer agents, may reduce 
      tumor cell resistance against immune responses. The authors tested whether 
      treatment with gemcitabine or cyclooxygenase-2 (COX-2) inhibitors increases the 
      sensitivity of pancreatic carcinoma cells to CTL-mediated killing. 
      Monocyte-derived DCs of HLA-A2+ donors were loaded with lysate from the HLA-A2+ 
      pancreatic carcinoma cell line Panc-1 and co-cultured with autologous CD3+ T 
      cells. ELISPOT and cytotoxicity assays performed after two rounds of in vitro 
      stimulation confirmed induction of a tumor-specific CTL response. Changes in the 
      magnitude and the effector mechanism of the CTL response were analyzed after 
      treatment of Panc-1 cells with gemcitabine and COX-2 inhibitors. Compared with 
      gemcitabine, COX-2 inhibitors more effectively sensitized Panc-1 cells to 
      CTL-mediated killing and showed less inhibition of T-cell activation by DCs in 
      vitro. Using anti-CD95 blocking antibody, the authors showed that the increase in 
      CTL-mediated tumor cell killing observed after treatment with COX-2 inhibitors is 
      dependent on CD95/CD95 ligand interaction. Increased apoptosis of Panc-1 cells 
      treated with COX-2 inhibitor was also observed after incubation with agonistic 
      anti-CD95 antibody. Sensitization of cancer cells to CD95-dependent killing by 
      CTLs represents a novel mechanism of action for COX-2 inhibitors and provides a 
      rationale for their concomitant use with immunotherapeutic strategies such as 
      DC-based vaccination.
FAU - Dauer, Marc
AU  - Dauer M
AD  - Section of Gastroenterology, Medizinische Klinik Innenstadt, University of 
      Munich, 80336 Munich, Germany.
FAU - Herten, Jan
AU  - Herten J
FAU - Bauer, Christian
AU  - Bauer C
FAU - Renner, Frederik
AU  - Renner F
FAU - Schad, Katharina
AU  - Schad K
FAU - Schnurr, Max
AU  - Schnurr M
FAU - Endres, Stefan
AU  - Endres S
FAU - Eigler, Andreas
AU  - Eigler A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Membrane Proteins)
RN  - 0 (fas Receptor)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Antigens, Neoplasm/*immunology
MH  - Cell Differentiation/immunology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Coculture Techniques
MH  - Cyclooxygenase 2
MH  - Cytokines/metabolism/pharmacology
MH  - Cytotoxicity, Immunologic/drug effects/*immunology
MH  - Dendritic Cells/*immunology
MH  - Deoxycytidine/analogs & derivatives/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Humans
MH  - Leukocytes, Mononuclear/cytology/drug effects
MH  - Lymphocyte Activation/drug effects
MH  - Membrane Proteins
MH  - Pancreatic Neoplasms/immunology/pathology
MH  - Prostaglandin-Endoperoxide Synthases
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Th1 Cells/immunology
MH  - fas Receptor/immunology
MH  - Gemcitabine
EDAT- 2005/07/08 09:00
MHDA- 2005/10/18 09:00
CRDT- 2005/07/08 09:00
PHST- 2005/07/08 09:00 [pubmed]
PHST- 2005/10/18 09:00 [medline]
PHST- 2005/07/08 09:00 [entrez]
AID - 00002371-200507000-00008 [pii]
AID - 10.1097/01.cji.0000164038.41104.f5 [doi]
PST - ppublish
SO  - J Immunother. 2005 Jul-Aug;28(4):332-42. doi: 10.1097/01.cji.0000164038.41104.f5.