The transcription factor RBP-J-mediated signaling is essential for dendritic cells to evoke efficient anti-tumor immune responses in mice

• Published in: Molecular cancer 2010-04, Vol.9 (1), p.90-90, Article 90
• Main Authors: Feng, Fan, Wang, Yao-Chun, Hu, Xing-Bin, Liu, Xiao-Wei, Ji, Gang, Chen, Yun-Ru, Wang, Lin, He, Fei, Dou, Guo-Rui, Liang, Liang, Zhang, Hong-Wei, Han, Hua
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - immunology; Biology; Cancer; Carcinoma, Lewis Lung; Care and treatment; Cell culture; Cell Separation; Dendritic cells; Dendritic Cells - immunology; Enzyme-Linked Immunosorbent Assay; Experiments; Flow Cytometry; Genetic aspects; Health aspects; Immunoglobulin J Recombination Signal Sequence-Binding Protein - immunology; Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism; Immunotherapy; Ligands; Lymphocyte Activation - immunology; Lymphocytes, Tumor-Infiltrating - immunology; Medical research; Melanoma; Melanoma, Experimental - immunology; Melanoma, Experimental - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Physiological aspects; Proteins; Receptors, Notch - immunology; Receptors, Notch - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Signal Transduction - immunology; Transcription factors; Tumors
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/1476-4598-9-90

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. 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. 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.