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

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.Dendritic cells (DCs) are professional antigen presenting cells (APCs) that initiate specific immune responses against pathogens [1] and tumor cells [2]. Immature DCs which locate in the tissues and the peripheral lymphoid organs persistently surveillance the environment and recognize the invading pathogens and cell debris [3], and capture antigens by phagocytosis, micropinocytosis, and endocytosis. After the antigen recognition and uptake, the immature DCs undergo a series of maturation events, including the up-regulation of the major histocompatibility complex (MHC) II and the co-stimulatory molecules, the secretion of cytokines, the outgrowth of dendrites, and the modulation of chemokine receptor expressi