PMID- 10786686
OWN - NLM
STAT- MEDLINE
DCOM- 20000511
LR  - 20220408
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 60
IP  - 8
DP  - 2000 Apr 15
TI  - CC chemokine receptor-7 on dendritic cells is induced after interaction with 
      apoptotic tumor cells: critical role in migration from the tumor site to draining 
      lymph nodes.
PG  - 2209-17
AB  - Dendritic cells (DCs) are very potent antigen-presenting cells and play critical 
      roles in regulating immune responses in cancer. The migrating of DCs from the 
      tumor site to the lymphoid organs is believed to be one of the critical events. 
      To examine this important DC function in tumor situations, bone marrow-derived 
      DCs, cultured for 6 days with granulocyte macrophage colony-stimulating factor 
      and interleukin 4, were inoculated at the tumor site. We have shown (Y. Nishioka 
      et al., Cancer Res., 59: 40354041, 1999) that DCs can migrate from tumor site to 
      the draining lymph nodes within 24 h (approximately 0.1% of administrated DCs). 
      The DCs then form clusters with adjacent lymphoid cells, which produce IFN-gamma 
      (1500-3200pg/10(6) cells/48 h) in response to tumor stimulation. The number of 
      the DCs migrating into lymph nodes were greater when they were inoculated into 
      the tumor rather than the skin. Coculture of DCs and apoptotic tumor cells 
      resulted in decreased expression of CC chemokine receptor (CCR) 1 and increased 
      CCR7 expression at mRNA level without alteration in other phenotypical markers on 
      DCs. Chemotaxis assay showed that CCR7 ligands, macrophage inflammatory protein 
      3beta and secondary lymphoid-tissue chemokine significantly (P < 0.05) induced 
      the migration of DCs when cocultured with apoptotic tumor cells. To directly 
      examine the involvement of CCR7 expression in DC migration, we investigated the 
      functions of DCs genetically modified to express high levels of CCR7. CCR7 
      transduction promotes DC migration in response to relevant ligands in vitro and 
      in vivo. These results suggest that the CCR7 expression of DCs is enhanced with 
      direct contact with apoptotic tumor cells and may have a critical role for DC 
      migrating to regional lymph nodes. The means to promote DC delivery to tumor and 
      to nodal sites represent novel targets for the biological therapy of cancer.
FAU - Hirao, M
AU  - Hirao M
AD  - Department of Surgery, School of Medicine, University of Pittsburgh Cancer 
      Institute, Pennsylvania 15213, USA.
FAU - Onai, N
AU  - Onai N
FAU - Hiroishi, K
AU  - Hiroishi K
FAU - Watkins, S C
AU  - Watkins SC
FAU - Matsushima, K
AU  - Matsushima K
FAU - Robbins, P D
AU  - Robbins PD
FAU - Lotze, M T
AU  - Lotze MT
FAU - Tahara, H
AU  - Tahara H
LA  - eng
GR  - 1PO1 CA73743-01/CA/NCI NIH HHS/United States
GR  - P01 CA59371/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Ccr1 protein, mouse)
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokines, CC)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR1)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Animals
MH  - *Apoptosis/radiation effects
MH  - *Cell Movement/drug effects
MH  - Chemokine CCL4
MH  - Chemokines, CC/pharmacology
MH  - Coculture Techniques
MH  - Dendritic Cells/cytology/drug effects/*immunology/transplantation
MH  - Female
MH  - Fibrosarcoma/immunology/*pathology
MH  - Flow Cytometry
MH  - *Gene Expression Regulation, Neoplastic
MH  - Lymph Nodes/drug effects/immunology
MH  - Macrophage Inflammatory Proteins/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, CCR1
MH  - Receptors, CCR7
MH  - Receptors, Chemokine/*genetics/immunology
MH  - Th1 Cells/immunology
MH  - Transduction, Genetic
MH  - Tumor Cells, Cultured
MH  - Ultraviolet Rays
EDAT- 2000/04/29 09:00
MHDA- 2000/05/16 09:00
CRDT- 2000/04/29 09:00
PHST- 2000/04/29 09:00 [pubmed]
PHST- 2000/05/16 09:00 [medline]
PHST- 2000/04/29 09:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2000 Apr 15;60(8):2209-17.