How do immune checkpoint inhibitors work?

Immune checkpoint inhibitors are drugs that block the inhibitory (negative) signals founds on immune cells and which act as a brake on these cells sending them to a stationary state. These are molecules like PD-1 and CTLA-4 whose amount goes up when immune cells get activated. If we think about it, this phenomenon is important for taming the immune system following a phase of activation so it does not go uncontrolled.

Immune checkpoint inhibitors form the main type of cancer immunotherapy. Examples of these drugs include the anti-PD-1 antibodies Keytruda® (pembrolizumab) and Opdivo® (nivolumab) and  the anti-CTLA-4 antibody Yervoy® (ipilimumab).

When immune checkpoints like PD-1 and CTLA-4 are blocked we create a situation similar to releasing the brake in a car allowing it to get on the move again.

In the context of cancer, this means the immune cells recover their ability to act against and kill tumors. This also means that most other immune cells in the body are in a state of prolonged activation which is why treatment with checkpoint inhibitors creates a situation akin to having an auto-immune disease.

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1 thought on “How do immune checkpoint inhibitors work?

  1. Thanks for a clear and concise explanation of the mechanisms behind immune checkpoint inhibitor therapy.
    It’s much appreciated.
    The graphic was also helpful.

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