PMID- 20420708
OWN - NLM
STAT- MEDLINE
DCOM- 20100730
LR  - 20220408
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 9
DP  - 2010 Apr 27
TI  - The transcription factor RBP-J-mediated signaling is essential for dendritic 
      cells to evoke efficient anti-tumor immune responses in mice.
PG  - 90
LID - 10.1186/1476-4598-9-90 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) are professional antigen presenting cells that 
      initiate specific immune responses against tumor cells. Transcription factor 
      RBP-J-mediated Notch signaling regulates DC genesis, but whether this pathway 
      regulates DC function in anti-tumor immunity remains unclear. In the present work 
      we attempted to identify the role of Notch signaling in DC-mediated anti-tumor 
      immune response. RESULTS: When DCs were co-inoculated together with tumor cells, 
      while the control DCs repressed tumor growth, the RBP-J deficient DCs had lost 
      tumor repression activity. This was most likely due to that DCs with the 
      conditionally ablated RBP-J were unable to evoke anti-tumor immune responses in 
      the solid tumors. Indeed, tumors containing the RBP-J deficient DCs had fewer 
      infiltrating T-cells, B-cells and NK-cells. Similarly, the draining lymph nodes 
      of the tumors with RBP-J-/- DCs were smaller in size, and contained fewer cells 
      of the T, B and NK lineages, as compared with the controls. At the molecular 
      level, the RBP-J deficient DCs expressed lower MHC II, CD80, CD86, and CCR7, 
      resulting in inefficient DC migration and T-cell activation in vitro and in vivo. 
      T-cells stimulated by the RBP-J deficient DCs did not possess efficient 
      cytotoxicity against tumor cells, in contrast to the control DCs. CONCLUSION: The 
      RBP-J-mediated Notch signaling is essential for DC-dependent anti-tumor immune 
      responses. The deficiency of RBP-J impairs the DC-based anti-tumor immunity 
      through affecting series of processes including maturation, migration, antigen 
      presentation and T-cell activation. The Notch signaling pathway might be a target 
      for the establishment of the DC-based anti-tumor immunotherapies.
FAU - Feng, Fan
AU  - Feng F
AD  - Department of Medical Genetics and Developmental Biology, State Key Laboratory of 
      Cancer Biology, Fourth Military Medical University, 15 West Changle Road, Xi'an, 
      710032, China.
FAU - Wang, Yao-Chun
AU  - Wang YC
FAU - Hu, Xing-Bin
AU  - Hu XB
FAU - Liu, Xiao-Wei
AU  - Liu XW
FAU - Ji, Gang
AU  - Ji G
FAU - Chen, Yun-Ru
AU  - Chen YR
FAU - Wang, Lin
AU  - Wang L
FAU - He, Fei
AU  - He F
FAU - Dou, Guo-Rui
AU  - Dou GR
FAU - Liang, Liang
AU  - Liang L
FAU - Zhang, Hong-Wei
AU  - Zhang HW
FAU - Han, Hua
AU  - Han H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100427
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
RN  - 0 (Rbpj protein, mouse)
RN  - 0 (Receptors, Notch)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - Carcinoma, Lewis Lung
MH  - Cell Separation
MH  - Dendritic Cells/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Immunoglobulin J Recombination Signal Sequence-Binding 
      Protein/*immunology/metabolism
MH  - Lymphocyte Activation/immunology
MH  - Lymphocytes, Tumor-Infiltrating/immunology
MH  - Melanoma, Experimental/*immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Receptors, Notch/immunology/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*immunology
PMC - PMC2867822
EDAT- 2010/04/28 06:00
MHDA- 2010/07/31 06:00
PMCR- 2010/04/27
CRDT- 2010/04/28 06:00
PHST- 2010/02/04 00:00 [received]
PHST- 2010/04/27 00:00 [accepted]
PHST- 2010/04/28 06:00 [entrez]
PHST- 2010/04/28 06:00 [pubmed]
PHST- 2010/07/31 06:00 [medline]
PHST- 2010/04/27 00:00 [pmc-release]
AID - 1476-4598-9-90 [pii]
AID - 10.1186/1476-4598-9-90 [doi]
PST - epublish
SO  - Mol Cancer. 2010 Apr 27;9:90. doi: 10.1186/1476-4598-9-90.