Immune T Cell Pathway Critical for Tumor Control

Immune T Cell Pathway Critical for Tumor Control

T cellA 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.

Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.