Inhibitory Receptors

Inhibitory receptors are a type of protein found on the surface of immune cells, such as T cells and NK (Natural Killer) cells, white blood cells that serve as a critical first line of defense. They are sometimes called negative receptors. Their role is to slow down, suppress, or switch off cellular activity in response to specific signals. In essence, they are “off-switches” designed to prevent harmful overactivation of the immune system.

What is their central role in the immune system?

Inhibitory receptors are essential for maintaining immune balance in two main ways.
They prevent autoimmunity by helping stop the immune system from attacking the body’s own tissues.
They also regulate inflammation by controlling the strength and duration of inflammatory responses, preventing them from turning chronic.

How are inhibitory receptors connected to immune cell exhaustion?

The best-known example of an inhibitory receptor is PD-1. When a T cell encounters a tumor, it begins to express high levels of PD-1. Cancer cells exploit this by expressing the ligand, the protein that binds PD-1. When the ligand attaches to the receptor, it sends a strong inhibitory signal into the T cell, pushing it into exhaustion and shutting down its ability to attack.

Why are inhibitory receptors important in cancer therapy?

Blocking these receptors is the foundation of the immunotherapy revolution. Checkpoint inhibitors, a breakthrough class of cancer drugs, work by blocking inhibitory receptors such as PD-1. By releasing the brake, the treatment allows exhausted immune cells to “wake up” and resume their attack on the tumor. In the laboratory of Prof. Mira Barda-Saad at the Dangoor Center, researchers are developing therapies that use inhibitory-receptor blockade to prevent various types of cancer.