title: T cell-NF-κB activation is required for tumor control in vivo.
abstract: BACKGROUND
  T cells have the capacity to eliminate tumors but the signaling pathways by which they do so are incompletely understood. T cell priming requires activation of the transcription factors AP-1, NFAT and NF-κB downstream of the TCR, but whether activation of T cell-NF-κB in vivo is required for tumor control has not been addressed. In humans and mice with progressively growing tumors, the activity of T cell-intrinsic NF-κB is often reduced. However, it is not clear if this is causal for an inability to reject transformed cells, or if it is a consequence of tumor growth. T cell-NF-κB is important for T cell survival and effector differentiation and plays an important role in enabling T cells to reject cardiac and islet allografts, suggesting the possibility that it may also be required for tumor elimination. In this study, we tested whether normal T cell-NF-κB activation is necessary for the rejection of tumors whose growth is normally controlled by the immune system.
  
  
  METHODS
  Mice with genetically impaired T cell-NF-κB activity were subcutaneously injected with MC57-SIY tumor cells. Tumor growth was measured over time, and the anti-tumor immune response was evaluated using flow cytometry and cytokine detection assays.
  
  
  RESULTS
  Mice with impaired T cell-NF-κB activity were unable to reject tumors that were otherwise eliminated by wildtype mice, despite equal accumulation of tumor-reactive T cells. In addition, specific impairment of NF-κB signaling downstream of the TCR was sufficient to prevent tumor rejection. Tumor antigen-specific T cell-IFN-γ and TNF-α production, as well as cytotoxic ability, were all reduced in mice with impaired T cell-NF-κB, suggesting an important role for this transcription factor in the effector differentiation of tumor-specific effector T cells.
  
  
  CONCLUSIONS
  Our results have identified the NF-κB pathway as an important signaling axis in T cells, required for the elimination of growing tumors in vivo. Maintaining or enhancing T cell-NF-κB activity may be a promising avenue for anti-tumor immunotherapy.
authors: Department of Medicine, The University of Chicago, 924 E. 57th St. JFK-R312, Chicago, IL 60637 USA.
authors: Sarah E
authors: SE
authors: Barnes
authors: Department of Medicine, The University of Chicago, 924 E. 57th St. JFK-R312, Chicago, IL 60637 USA.
authors: Ying
authors: Y
authors: Wang
authors: Department of Medicine, The University of Chicago, 924 E. 57th St. JFK-R312, Chicago, IL 60637 USA.
authors: Luqiu
authors: L
authors: Chen
authors: Genentech, Inc., 1 DNA Way MS: 245c, South San Francisco, CA 94080 USA.
authors: Luciana L
authors: LL
authors: Molinero
authors: Department of Medicine, The University of Chicago, 924 E. 57th St. JFK-R312, Chicago, IL 60637 USA ; Department of Pathology, The University of Chicago, 927 E. 57th St, Chicago, IL 60637 USA.
authors: Thomas F
authors: TF
authors: Gajewski
authors: Department of Medicine, The University of Chicago, 924 E. 57th St. JFK-R312, Chicago, IL 60637 USA.
authors: Cesar
authors: C
authors: Evaristo
authors: Department of Medicine, The University of Chicago, 924 E. 57th St. JFK-R312, Chicago, IL 60637 USA.
authors: Maria-Luisa
authors: ML
authors: Alegre
keywords: Cytokine production; Cytotoxicity; Effector function; NF-κB; Priming; T cell; Tumor rejection
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