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The human immune system is a complex and closely regulated system. This system includes several immune checkpoints. These checkpoints prevent an immune response from being too strong which could damage healthy cells in the body. Immune checkpoints are activated when checkpoint proteins on the surface of T-lymphocytes (a type of white blood cells) recognize and bind to partner proteins on other cells, such as cancer cells. When the checkpoint and partner proteins bind together, an “off” signal is sent to the T-cells, protecting the partner cell from immune destruction. Cancer cells exploit this mechanism by expressing many partners for checkpoint proteins on their cell surface, which allows them to evade elimination by the immune system.

Immune checkpoint inhibitors (ICIs), a form of immunotherapy, block the binding of checkpoint proteins to partner proteins, preventing the creation of an “off” signal and allowing the T-cells to kill cancer cells. As such, ICIs are able to re-activate the immune response to cancer cells.

The most important checkpoint proteins from a therapeutic point of view consist of programmed-death 1 (PD-1) and its partner protein PD-L1. For the moment, two inhibitors of this checkpoint are being used in the treatment of classical Hodgkin lymphoma: nivolumab and pembrolizumab.

Although ICIs are considered less toxic than chemotherapy, also ICIs come with a specific set of side effects. Among the more common side effects of these agents are rash, fatigue, and diarrhea. In addition to this, ICIs can be associated with rare, but potentially irreversible and even life-threatening immune-related side effects. These include diabetes caused by an inflammation of the pancreas, hepatitis (inflammation of the liver), hypophysitis (inflammation of the pituitary gland), myocarditis (inflammation of the heart muscle), an impaired kidney function, an over- or underactive thyroid and problems with the nervous system (e.g., muscle weakness, numbness).

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