Checkpoint Inhibitors Explained

This page is for anyone who has been offered a checkpoint inhibitor, a type of immunotherapy. It explains how these drugs work, which cancers they treat, and which side effects to watch for.

Your immune system has built-in brakes. They are called immune checkpoints, and they are a normal part of the system. Their job is to keep an immune response from getting so strong that it destroys healthy cells.

The problem is that some cancers learn to use those brakes to protect themselves. Immune checkpoint inhibitors are a type of immunotherapy. They release the brakes, so your immune system can fight the cancer.

Checkpoint inhibitors take the brakes off your immune system so it can attack cancer.

Immune cells called T cells carry proteins on their surface. Those proteins can bind to partner proteins on other cells, including some tumor cells. Together they are called immune checkpoint proteins.

When a checkpoint protein binds its partner, the pair sends an off signal to the T cell. In healthy tissue that off signal protects you. It stops the immune system from attacking your own cells. But a tumor can send the same off signal. Then the immune system does not destroy the cancer.

Immune checkpoint inhibitors block checkpoint proteins from binding their partner proteins. The off signal never gets sent. That leaves the T cells free to kill cancer cells.

Different drugs target different checkpoints:

• One type acts against a checkpoint protein called CTLA-4.
• Others act against a checkpoint protein called PD-1, or its partner protein PD-L1.

Some tumors make a lot of PD-L1 to turn down the T cell response. Blocking PD-1 or PD-L1 can free the T cells to attack.

Checkpoint inhibitors are approved to treat some people with many cancer types. They include:

• breast cancer
• bladder cancer
• cervical cancer
• colon cancer
• head and neck cancer
• Hodgkin lymphoma
• liver cancer
• lung cancer
• renal cell cancer, a type of kidney cancer
• skin cancer, including melanoma
• stomach cancer
• rectal cancer
• any solid tumor that cannot repair certain errors in its DNA

Checkpoint inhibitors affect people in different ways. What you get depends on several things:

• How healthy you are before treatment.
• Your type of cancer, and how advanced it is.
• The drug you receive, and the dose.

Doctors and nurses cannot know for sure whether side effects will happen, when, or how serious they will be. So it helps to know the signs to watch for.

Common side effects include:

• rash
• diarrhea
• fatigue

Rarer side effects can include inflammation in different organs. What it looks like depends on the organ involved:

• Skin: changes and itching.
• Lungs: cough and chest pain.
• Colon: belly pain and diarrhea.
• Pancreas: diabetes.
• Liver: hepatitis (liver inflammation).

Problems can also show up in the pituitary gland, heart muscle, kidneys, thyroid, or nervous system.

Because side effects can involve inflammation in different organs, report new symptoms to your team quickly.

• Call 911 or go to an emergency department if you have chest pain, a pounding or racing heart, or you are fighting for breath. NCI lists myocarditis and lung inflammation among the rarer effects of these drugs. Do not drive yourself.
• Call your care team right away if a new cough starts, stairs leave you short of breath, or belly pain comes with watery stools. Call right away too if your eyes or skin look yellow, or you feel new muscle weakness or numbness. These can be signs of inflammation in the lungs, colon, liver or nerves. For emergencies call 911 or go to the ER.
• Call your care team right away if your temperature is 100.4°F (38°C) or higher. If a checkpoint inhibitor is being given alongside chemotherapy, CDC calls a fever during chemotherapy a medical emergency.
• Call your care team within a day or two if a rash spreads or itching keeps you awake. These can be early signs of skin inflammation.