An international research team has discovered a gene that triggers a process called “exhaustion” in the immune T cells used to battle cancer in immunotherapy. The gene, called Tox, launches a process that remodels the cells’ machinery to weaken their ability to attack cancer cells, as well as infections. Such immunotherapy—in which a cancer patient’s own immune cells are activated to detect tell-tale proteins called antigens on cancer cells—is highly promising. However, T cell exhaustion has proven a daunting barrier to the therapy.
The discovery, published in advance online in the journal Nature, could lead to diagnostic tests to detect T cell exhaustion, and the researchers hope their basic findings will also result in techniques to prevent exhaustion.
Among lead researchers on the team was Ben Youngblood, Ph.D., an assistant member of the St. Jude Department of Immunology. Besides Youngblood, the other team leaders were Dietmar Zehn of the Technical University of Munich, Germany, and Robert Thimme of the University of Freiburg, Germany. Other co-authors were, from St. Jude: Hazem Ghoneim and Yiping Fan; from the Technical University of Munich: Francesca Alfei, Kristiyan Kanev, Ming Wu, Madlaina von Hösslin, Jolie Cullen, Dirk Wohlleber, and Katja Steiger; from the University of Freiburg: Maike Hofmann and Robert Thimme; from the University of Lausanne, Switzerland, Patrick Roelli and Mauro Delorenzi; from the University of Melbourne, Australia: Daniel Utzschneider; from Bar-Ilan University, Israel: Vasyl Eisenberg and Cyrille Cohen; and from the University, Switzerland: Doron Merkler.
The research was supported by the European Research Council, the Swiss National Science Foundation, the Swiss Vaccine Research Institute, the German Research Foundation, German-Israeli Foundation for Scientific Research and Development, the Germany Center for Infection Research Munich site, the National Institutes of Health (R01AI114442) and ALSAC, fundraising and awareness arm of St. Jude.