One of the best tools your body has to stay healthy is your immune system. This sophisticated 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 difficult because some cancer cells learn to hide from the immune system so that they are not recognized as a threat. When this happens, your immune system may not recognize them as an enemy and may not attack them as it should.
Immunotherapy is a form of treatment that helps your immune system better fight cancer. It strengthens your immune system and helps it recognize and attack the real threat. An important type of immunotherapy are so-called immune checkpoint inhibitors. These are medications 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 tries to attack foreign cells, it reacts so violently that it kills healthy cells too.
Immune checkpoints are a type of natural “brake” that helps 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 apply the “brakes” of the immune system. When these proteins on cancer cells combine with certain proteins on immune cells, the immune system is turned off. This prevents the immune cells from attacking the cancer cells and allows the cancer to grow and spread.
Immune checkpoint inhibitors block this connection. If the “brakes” cannot be applied, the immune system remains vigilant 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 lasts about 30 to 60 minutes, but you will likely need several infusion sessions over the course of your treatment.
What different types of immune checkpoint inhibitors are there?
There are different types of immune checkpoint inhibitors. Each of them targets a different “off switch” in the immune system.
PD-1 and PD-L1 inhibitors: T cells, also known as fight cells, have a protein called PD-1 that stops them from attacking healthy cells. Healthy cells have a matching protein called PD-L1. When PD-1 and PD-L1 combine, the immune response is turned off.
Some cancer cells also have PD-L1 proteins, which trick the immune system into shutting down, allowing the cancer cells to grow. PD-1 and PD-L1 inhibitors block this connection, preventing the cancer cells from turning off the immune response so that T cells can continue fighting the cancer.
CTLA-4 inhibitors: Like PD-1, CTLA-4 is another protein on T cells that turns off the immune response and acts like an off switch for the immune system. CTLA-4 inhibitors block this switch, preventing the checkpoint from being turned off, allowing T cells to continue fighting the cancer. This type of inhibitor is often used together with PD-1 and PD-L1 inhibitors in certain types of cancer.
LAG-3 inhibitors: LAG-3 is a checkpoint protein found on various types of immune cells, including T cells. It also acts as an off switch to prevent the immune system from attacking healthy cells. LAG-3 inhibitors prevent the checkpoints from turning off the immune system, allowing immune cells to continue attacking cancer cells. Currently, this type of inhibitor (called relatlimab) is used together with the PD-1 inhibitor nivolumab to treat melanoma. Researchers are studying whether they can also help treat other types of cancer.
What are the most common side effects of immune checkpoint inhibitors?
Because immune checkpoint inhibitors activate the immune system, they can sometimes cause inflammation in almost every organ. These problems are called immune-related adverse events (irAEs).
They can range from mild symptoms such as a rash or fever to more serious problems such as inflammation of the stomach and intestines or, in rare cases, the heart. Most side effects are mild, but serious and even life-threatening reactions can occur. Therefore, it is important that you report any new symptoms to your care team immediately.
The most common side effects of an immune checkpoint inhibitor are rash, diarrhea, fatigue, and thyroid complications, but all sorts of side effects can also be caused by inflammation. These side effects may include:
- Rash, itching, skin color changes – skin toxicity (dermatitis)
- Cough or difficulty breathing – pneumonia (pneumonitis)
- Chest pain – inflammation of the heart (myocarditis) or inflammation of the lining of 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), which can affect insulin production
- Thyroid problems – overactive or underactive thyroid (thyroiditis)
- Hypophysitis – Inflammation of the pituitary gland that can affect hormone levels
- Nephritis – inflammation of the kidneys
- Muscle weakness or numbness – inflammation of the nerves or muscles (neuropathy or myositis)
How are immune checkpoint inhibitors used to treat cancer?
Since the approval of the first immune checkpoint inhibitor in 2011, these drugs have become an important part of cancer treatment. Today, there are more than 100 approved uses for various checkpoint inhibitors. They are used to treat many types of cancer, including breast, lung, stomach, skin, kidney, and various blood cancers, among others.
These medicines were initially used primarily for metastatic cancer, i.e. 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. Today, immune checkpoint inhibitors are used for:
- Adjuvant setting – treatment after surgery to reduce the risk of the cancer coming back
- Neoadjuvant setting – treatment before surgery to shrink the tumor and improve outcomes
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 have already received, and your general health.
Because these medications activate the immune system, it is very important to monitor for new or changed symptoms during treatment. Identifying side effects early will help your care team treat them quickly and prevent more serious problems.
Learning to recognize these symptoms – and informing your care team immediately – is an essential part of staying safe during immunotherapy.
This educational resource was created with support from Merck.
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