title: The transcription factor RBP-J-mediated signaling is essential for dendritic cells to evoke efficient anti-tumor immune responses in mice.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.forename: Yao-Chun
authors.initials: YC
authors.lastname: Wang
authors.forename: Xing-Bin
authors.initials: XB
authors.lastname: Hu
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Ji
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.forename: Guo-Rui
authors.initials: GR
authors.lastname: Dou
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018827:Carcinoma, Lewis Lung; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D051880:Receptors, Notch