One of the best tools your body has for staying healthy is your immune system. This elaborate, protective force within you is designed to seek out and destroy enemy cells (things that don’t belong) such as viruses, bacteria and sometimes cancer cells. However, cancer can be tricky because some cancer cells learn how to hide from the immune system so they are not identified as a threat. When this happens, your immune system may not recognize them as the enemy and may not attack them the way it should.
Immunotherapy is a type of treatment that helps your immune system work better against cancer. It boosts your immune system to help it find and attack the real threat. One important kind of immunotherapy is called immune checkpoint inhibitors, which are drugs that help your immune system “see” cancer cells more clearly so it can attack them.
Here’s what you need to know about immune checkpoint inhibitors.
What is an immune checkpoint?
Your immune system is designed to attack things that don’t belong in your body. But, sometimes, when your immune system is trying to target foreign cells, it has such a strong reaction that it kills healthy cells too.
Immune checkpoints are kind of like natural “brakes” that help control the immune system. They help turn the immune response on and off as needed, so your body doesn’t accidentally attack itself.
How do immune checkpoint inhibitors work?
Immune checkpoint inhibitors help the immune system stay active so it can fight cancer cells more effectively.
Some cancer cells use special proteins to press the immune system’s “brakes.” When these proteins on cancer cells connect with certain proteins on immune cells, the immune system gets turned off. This stops the immune cells from attacking the cancer cells and allows the cancer to grow and spread.
Immune checkpoint inhibitors block this connection. When the “brakes” can’t be turned on, the immune system stays alert and can attack the cancer cells.
Most immune checkpoint inhibitors are given as a liquid infusion through a vein. Some are given as an injection under the skin. A typical infusion session will last about 30 to 60 minutes, but you will likely need several infusion sessions during the course of your treatment.
What are the different types of immune checkpoint inhibitors?
There are several types of immune checkpoint inhibitors. Each one targets a different “off switch” in the immune system.
PD-1 and PD-L1 inhibitors: T cells, also called fighter cells, have a protein called PD-1 that helps keep them from attacking healthy cells. Healthy cells have a matching protein called PD-L1. When PD-1 and PD-L1 connect, the immune response turns off.
Some cancer cells also have PD-L1 proteins that trick the immune system into turning off, which allows the cancer cells to grow. PD-1 and PD-L1 inhibitors block this connection, stopping the cancer cells from turning the immune response off so T cells can keep fighting the cancer.
CTLA-4 inhibitors: Like PD-1, CTLA-4 is another protein on T cells that turn the immune response off, working like an off switch for the immune system. CTLA-4 inhibitors block this switch, stopping the checkpoint from turning off so T cells can keep fighting the cancer. This type of inhibitor is often used together with PD-1 and PD-L1 inhibitors for certain cancers.
LAG-3 inhibitors: LAG-3 is a checkpoint protein found on several types of immune cells, including T cells. It also works as an off switch to keep the immune system from attacking healthy cells. LAG-3 inhibitors stop the checkpoints from turning off so the immune cells can keep attacking cancer cells. Right now, this type of inhibitor (called relatlimab) is used with the PD-1 inhibitor called nivolumab to treat melanoma. Researchers are studying whether they can help treat other cancers as well.
What are the common side effects of immune checkpoint inhibitors?
Because immune checkpoint inhibitors activate the immune system, they can sometimes cause inflammation in almost any organ. These problems are called immune-related adverse events (irAEs).
They can range from mild issues — like a rash or fever — to more serious problems, such as inflammation in the stomach and intestines or, in rare cases, the heart. Most side effects are mild, but serious and even life-threatening reactions can happen, so it’s important to report any new symptoms to your care team right away.
The most common side effects of an immune checkpoint inhibitor are rash, diarrhea, fatigue and thyroid complications, but all kinds of side effects can result from inflammation. These side effects can include:
- Rash, itchiness, changes in skin color — skin toxicity (dermatitis)
- Cough or trouble breathing — lung inflammation (pneumonitis)
- Chest pain — heart inflammation (myocarditis) or inflammation of the lining around the heart (pericarditis)
- Nausea, diarrhea or stomach pain — inflammation of the stomach or intestines (gastritis, colitis)
- Hepatitis — inflammation of the liver
- New diabetes — inflammation of the pancreas (pancreatitis) that can affect insulin production
- Thyroid problems — overactive or underactive thyroid (thyroiditis)
- Hypophysitis — inflammation of the pituitary gland, which can affect hormone levels
- Nephritis — inflammation of the kidneys
- Muscle and weakness or numbness — nerve or muscle inflammation (neuropathy or myositis)
How are immune-checkpoint inhibitors used to treat cancer?
Since the first immune checkpoint inhibitor was approved in 2011, these medicines have become an important part of cancer treatment. Today, there are more than 100 approved uses for different checkpoint inhibitors. They are used to treat many types of cancer, including breast, lung, stomach, skin, kidney and several blood cancers, among others.
These medicines were first used mainly for metastatic cancer, which means cancer that has spread to other parts of the body. Over time, research has shown that they can also help earlier in the course of the disease. Now, immune checkpoint inhibitors are used in the:
- Adjuvant setting — treatment given after surgery to lower the chance the cancer will come back
- Neoadjuvant setting — treatment given before surgery to help shrink the tumor and improve results
Whether your medical team recommends an immune checkpoint inhibitor depends on many factors, including the type of cancer you have, how advanced it is, what treatments you’ve already had and your overall health.
Because these medicines activate the immune system, it is very important to pay attention to any new or changing symptoms during treatment. Catching side effects early helps your care team treat them quickly and prevent more serious problems.
Learning how to recognize these symptoms — and letting your care team know right away — is a key part of staying safe while receiving immunotherapy.
This educational resource was created with support from Merck.