Immune Cell Exhaustion

Immune cells are the body’s defenders against invading organisms. Immune cell exhaustion is a state in which these cells can no longer carry out their full protective functions. This phenomenon appears especially in T cells, and it develops when they are exposed to an antigen (an invading threat) continuously over a long period. Although exhaustion is an adaptive mechanism meant to prevent damage from chronic inflammation, in situations like cancer it becomes harmful, because it leaves the immune system unable to fight effectively.

How does T-cell exhaustion develop?

Exhaustion emerges gradually in response to ongoing antigenic stimulation, a constant “attack signal” coming from the disease. In conditions such as chronic viral infections or cancer, T cells, which are the spearhead of the cellular immune response, slowly lose their ability to produce killing molecules (cytokines) and their capacity to multiply and renew themselves.

What are the molecular features of T-cell exhaustion?

The most striking feature is the appearance of many inhibitory receptors on the surface of exhausted T cells. These receptors act like brakes. When they bind to matching proteins on tumor cells, they send a strong “stop” signal that shuts down the T cell’s activity.

Can an exhausted T cell be restored to normal function?

Yes. Restoring the cell’s activity is the foundation of immunotherapy. This breakthrough treatment, known as checkpoint inhibition, works by blocking those inhibitory receptors.

Once the brakes are lifted, the exhausted T cell can “wake up” and resume its attack on cancer cells. This approach has also been studied and developed in the laboratory of Prof. Mira Barda-Saad at the Dangoor Center for Personalized Medicine.