Immune Checkpoint Inhibitors and Their Side Effects
The immune system uses checkpoint proteins on immune cells to tell the difference between normal cells and those it sees as foreign, such as germs and cancer cells. These checkpoints act like switches that turn immune responses on or off, helping the body avoid attacking its own tissues.
Some cancer cells find ways to use these checkpoints to avoid being recognized and destroyed. Immune checkpoint inhibitors block the signals from these checkpoints, allowing the immune system to find and attack the cancer cells.
What are immune checkpoint inhibitors?
An immune checkpoint inhibitor (or just checkpoint inhibitor) is a type of monoclonal antibody, a lab-made protein designed to block checkpoint proteins that act like switches to turn the immune response on or off.
Checkpoint inhibitors don't kill cancer cells directly. They work by helping the immune system to better find and attack the cancer cells, wherever they are in the body. Medicines that target different checkpoint proteins are now used to treat many types of cancer.
Most of these drugs are given as an infusion into a vein (IV). A few of them can be given as an injection under the skin (subcutaneously) over several minutes as well. Your doctor will recommend which way of giving the checkpoint inhibitor is best for you.
PD-1 and PD-L1 inhibitors
PD-1 is a checkpoint protein on immune cells called T cells. It acts as a “off switch” to helps keep the T cells from attacking normal cells. PD-1 does this by attaching to PD-L1, a protein found on some normal and cancer cells. When PD-1 binds to PD-L1, it tells the T cell not to attack. Some cancer cells have large amounts of PD-L1, which helps them avoid being attacked by the immune system.
Monoclonal antibodies that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells.
Drugs that target PD-1 include:
- Pembrolizumab (Keytruda)
- Nivolumab (Opdivo and Opdivo Qvantig)
- Cemiplimab (Libtayo)
Drugs that target PD-L1 include:
- Atezolizumab (Tecentriq and Tecentriq Hybreza)
- Avelumab (Bavencio)
- Durvalumab (Imfinzi)
Both PD-1 and PD-L1 inhibitors have been shown to be helpful in treating many different types of cancer.
CTLA-4 inhibitors
CTLA-4 is another checkpoint protein on some T cells that acts as an “off switch” to help keep the immune system in check.
Ipilimumab (Yervoy) and tremelimumab (Imjuno) are monoclonal antibodies that attach to CTLA-4 and stop it from working. This can help boost the body’s immune response against cancer cells.
These drugs are typically used along with a PD-1 or PD-L1 inhibitor to treat several types of cancer.
LAG-3 inhibitors
LAG-3 is a checkpoint protein on some types of immune cells that normally acts as an “off switch” to help keep the immune system in check.
Relatlimab is a monoclonal antibody that attaches to LAG-3 and stops it from working. This can help boost the body’s immune response against cancer cells.
This drug is given along with the PD-1 inhibitor nivolumab (in a combination known as Opdualag). It can be used to treat melanoma of the skin, and it’s being studied for use in several other types of cancer.
Side effects of checkpoint inhibitors
Side effects of checkpoint inhibitors vary from person to person and drug to drug. You may hear these referred to as immune-related adverse events by your care team. They also can range from mild to severe, and quick recognition is important. Some of the more common side effects of checkpoint inhibitors include:
- Diarrhea
- Fatigue
- Cough
- Nausea and vomiting
- Skin rash
- Poor appetite
- Constipation
- Muscle and joint pain
Other, more serious side effects occur less often:
Infusion reactions: Some people might have an infusion reaction while getting these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting one of these drugs.
Autoimmune reactions: By targeting a checkpoint protein, these drugs remove one of the safeguards on the body's immune system. Sometimes the immune system responds by attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.
Cytokine release syndrome (CRS): As some types of checkpoint inhibitors, including nivolumab, destroy cancer cells, they can release large amounts of chemicals called cytokines into the blood, which can ramp up the immune system. Serious side effects from this release can include:
- High fever and chills
- Trouble breathing
- Severe nausea, vomiting, and/or diarrhea
- Feeling dizzy or lightheaded
- Headaches
- Fast heartbeat
- Feeling very tired
It’s very important to report any new side effects to someone on your health care team as soon as possible. If serious side effects do occur, treatment may need to be stopped and you might be given high doses of corticosteroids to suppress your immune system.
Your cancer care team will watch you closely during treatment and will check you often. Side effects can and should be treated as early as possible. It’s important to tell your cancer care team about any changes in how you feel or anything you notice that’s new or unusual. Tell them right away so they can treat any problems and try to keep them from getting worse.
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- References
Developed by the American Cancer Society medical and editorial content team with medical review and contribution by the American Society of Clinical Oncology (ASCO).
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Last Revised: July 7, 2025
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