PMID- 12353229
OWN - NLM
STAT- MEDLINE
DCOM- 20021107
LR  - 20171116
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 102
IP  - 1
DP  - 2002 Nov 1
TI  - Human dendritic cells induce tumor-specific apoptosis by soluble factors.
PG  - 20-8
AB  - Dendritic cells (DCs) are the most potent antigen producing cells (APCs) for 
      initiation of immune responses including anti-tumor immune responses. In previous 
      reports, it has been shown that DCs efficiently take up and process apoptotic or 
      necrotic bodies of tumor cells. It has also been shown that DCs pulsed with tumor 
      cell apoptotic bodies, lysates or peptides generate potent anti-tumor immune 
      responses. Direct interactions between DCs and viable tumor cells, however, have 
      not been clearly elucidated. We report that monocyte-derived, CD1a+ immature DCs 
      (iDCs) significantly inhibit the growth of breast tumor cells in coculture and 
      transwell experiments in the presence of soluble CD40 ligand (sCD40L), LPS or 
      both. The growth inhibition effects correlated with cell cycle arrest and 
      apoptosis of breast tumor cells. The effects were associated with morphological 
      changes of tumor cells from a round shape to a flat, spindle shape. In contrast, 
      no inhibition of proliferation or morphological changes was observed on normal 
      PBMC, K562 or breast fibroblasts. Interestingly, iDCs undergoing maturation 
      induced by sCD40L+LPS induced a much stronger growth inhibitory effect than iDCs 
      alone or mature DCs treated with sCD40L+LPS. Fractionation of supernatants showed 
      the anti-tumor effects were mediated by a TNF-alpha-dependent and -independent 
      mechanism. Soluble FasL and TRAIL were not involved. Our findings suggest that 
      maturing DCs have the intrinsic ability to induce cell-cycle arrest and apoptosis 
      of breast tumor cells through soluble factors, but not normal cells, in addition 
      to their Ag presentation function.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Joo, Hong-Gu
AU  - Joo HG
AD  - Department of Surgery and the Alvin J. Siteman Cancer Center, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Fleming, Timothy P
AU  - Fleming TP
FAU - Tanaka, Yoshiyuki
AU  - Tanaka Y
FAU - Dunn, Toby J
AU  - Dunn TJ
FAU - Linehan, David C
AU  - Linehan DC
FAU - Goedegebuure, Peter S
AU  - Goedegebuure PS
FAU - Eberlein, Timothy J
AU  - Eberlein TJ
LA  - eng
GR  - 2 T32 CA09621/CA/NCI NIH HHS/United States
GR  - R01 CA68500/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Annexin A5)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (CD40 Antigens)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - Annexin A5/metabolism
MH  - Antigen-Presenting Cells/immunology
MH  - *Apoptosis
MH  - Apoptosis Regulatory Proteins
MH  - Breast Neoplasms/*pathology
MH  - CD40 Antigens/metabolism
MH  - CD40 Ligand/pharmacology
MH  - Cell Cycle/physiology
MH  - Coculture Techniques
MH  - Dendritic Cells/drug effects/*physiology
MH  - Fibroblasts/pathology
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Membrane Glycoproteins/pharmacology
MH  - Monocytes/metabolism
MH  - Necrosis
MH  - RNA, Messenger/biosynthesis
MH  - T-Lymphocytes/immunology
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Tumor Cells, Cultured/pathology
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism/pharmacology
EDAT- 2002/09/28 04:00
MHDA- 2002/11/26 04:00
CRDT- 2002/09/28 04:00
PHST- 2002/09/28 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/09/28 04:00 [entrez]
AID - 10.1002/ijc.10656 [doi]
PST - ppublish
SO  - Int J Cancer. 2002 Nov 1;102(1):20-8. doi: 10.1002/ijc.10656.