Bar-Ilan University: Who Tells the Immune System to Slow Down?

Pr Cyrille J. Cohen Pr Cyrille J. Cohen

The primary task of the immune system is to defend the body against viruses, cancer cells and other pathogens.  T cells, a group of white blood cells which play a central role in immune response, recognize and target specific cells throughout the body that must be eliminated. They are the guardians of the body and can usually eliminate threats such as flu, chicken pox and other diseases within a few days.

Sometimes, however, infections can persist over the course of several months, causing chronic diseases. It is assumed that the same goes for cancer to which the immune system is constantly exposed. This puts tremendous pressure on the immune system, which on the one hand tries to actively eliminate these threats but on the other, limits its action so as not to cause collateral damage to healthy cells, chronic inflammation or autoimmune diseases. Thus, T-cells often enter a state of exhaustion, which slows down their activity, and they fail to fully get rid of a disease, such as in cancer.

Scientists have surmised that reversing this state of exhaustion may re-establish proper immunity. Indeed, this year’s Nobel Prize in Medicine was awarded to researchers who discovered the “molecular brakes” in T-cells that force T-cells to become exhausted. But until now the general mechanisms that orchestrate this have remained a mystery.

An international group of scientists from Germany, Switzerland, Australia, the United States, and Israel, led by Prof. Dietmar Zehn, of the Technological University of Munich, has elucidated part of this mechanism for the first time. 

“Thanks to this international collaboration, we demonstrated that the protein TOX is a master regulator of exhaustion state in T cells,” says Prof. Cyrille Cohen, a cancer immunologist at the Mina and Everard Goodman Faculty of Life Sciences at Bar-Ilan University, who participated in the study. “This protein, when active in T cells, is able to drive them into a state of severe non-responsiveness.”   

Cohen studied this phenomenon in human cells in a model of melanoma, successfully demonstrating a link between the expression of TOX in T-cells and the induction of hypo responsiveness, or diminished response to cancer. 

The study may provide researchers with a better understanding of how T cells are repressed and help them unlock their potential in fighting chronic diseases. “Now, with this information in hand we can think about how to neutralize some of these barriers so that we may restore the normal function of the immune system, even in chronic diseases, to better fight cancer or viral diseases,” concludes Cohen.

Published in Nature, June 17th 2019

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