Promoting T-Cell Survival

University of Pennsylvania researchers identify the protein TOX as crucial to the body’s response to T-cell exhaustion.


The immune cells known as effector T-cells fight both infectious agents and tumors by producing substances that kill harmful cells. Effector cells get tired, however, and become exhausted T-cells. Medical researchers have long desired to develop a way to prevent T-cells from becoming exhausted or converting those that do back into effector T-cells, particularly for developing chimeric antigen receptor T-cell (CAR-T) therapies and checkpoint-inhibitors.


Work from the University of Pennsylvania may make reaching that goal more likely. Researchers at the school have identified the TOX protein as playing a key role in determining the fate of exhausted T-cells.


The evolution of exhausted T-cells is controlled by the level of TOX. Sustained high levels of the protein promote the survival of exhausted T-cells at the expense of effector cells, which may allow tumors to remain or even grow. In addition, the genomes of T-cells are affected by TOX. In some cases, the genes are not able to produce proteins, which may be why it is difficult to convert exhausted T-cells into effector T-cells. The researchers believe these insights could be useful in developing new immunotherapies that target or engineer TOC to reverse or prevent exhaustion.


David Alvaro, Ph.D.

David is Scientific Editorial Director for That’s Nice and the Pharma’s Almanac content enterprise, responsible for directing and generating industry, scientific and research-based content, including client-owned strategic content. Before joining That’s Nice, David served as a scientific editor for the multidisciplinary scientific journal Annals of the New York Academy of Sciences. He received a B.A. in Biology from New York University and a Ph.D. in Genetics and Development from Columbia University.