A team led by researchers at The University of Chicago revealed an immune T cell signaling pathway crucial to controlling tumor growth in rodent models. The study was published in the Journal for Immunotherapy of Cancer and is entitled “T cell-NF-κB activation is required for tumor control in vivo.”
T cells specific to cancer antigens are known to play a central role in the elimination of growing tumors, although the mechanism and signaling pathways underlying such T cell ability are poorly understood.
The T cell receptor (TCR) in these cells’ surface is responsible for recognizing antigen molecules and consequently activate T cells. TCR signaling requires the activation of several transcription factors, including the nuclear factor-κ-light chain enhancer of activated B cells (NF-κB). The functional role played by NF-κB in tumor control is unknown, however.
Tumors can produce factors that inhibit TCR-induced NF-κB activation, and it has been reported that NF-κB activity, both in humans and mice, is often reduced in growing tumors; whether this is due to tumor expansion or a cause of T cells inability to control tumor growth is unclear. T cell-NF-κB is known to play a central role in the survival and proliferation of T cells, and also to be important in transplant organ rejection (rejection of cardiac and islet allografts).
In this study, normal T cell-NF-κB activation was assessed to determine its requirement for tumor elimination. Using genetic mouse models of NF-κB impairment in T cells, researchers injected tumor cells and followed tumor growth over time as well as the anti-tumor immune response.
It was found that mice with impaired T cell-NF-κB activity downstream of the TCR were incapable of rejecting tumors, when compared to wild-type control mice where tumors were eliminated. Both strains had a similar expansion and accumulation of tumor-specific T cells, although mice with impaired T cell-NF-κB activity exhibited decreased production of tumor antigen-specific T cell interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, and diminished cytotoxicity against tumor cells.
Researchers concluded that the T cell-NF-κB pathway is required for the successful elimination of growing tumors and plays an important role in the differentiation of tumor-specific effector T cells. The team believes that this signaling pathway could be a potential therapeutic target to improve anti-tumor therapy in cancer patients.