| First Author | Barnes SE | Year | 2015 |
| Journal | J Immunother Cancer | Volume | 3 |
| Issue | 1 | Pages | 1 |
| PubMed ID | 25648675 | Mgi Jnum | J:360992 |
| Mgi Id | MGI:7855079 | Doi | 10.1186/s40425-014-0045-x |
| Citation | Barnes SE, et al. (2015) T cell-NF-kappaB activation is required for tumor control in vivo. J Immunother Cancer 3(1):1 |
| abstractText | 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-kappaB downstream of the TCR, but whether activation of T cell-NF-kappaB 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-kappaB 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-kappaB 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-kappaB 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-kappaB 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-kappaB 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-kappaB signaling downstream of the TCR was sufficient to prevent tumor rejection. Tumor antigen-specific T cell-IFN-gamma and TNF-alpha production, as well as cytotoxic ability, were all reduced in mice with impaired T cell-NF-kappaB, 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-kappaB pathway as an important signaling axis in T cells, required for the elimination of growing tumors in vivo. Maintaining or enhancing T cell-NF-kappaB activity may be a promising avenue for anti-tumor immunotherapy. |
