The immune system protects the human body from viral and bacterial infections and cancer. Many different types of cells and mediators work together to attack and kill pathogens and cancer cells. Antibodies can be infused into the body to do the same. However, cancer cells have the ability to hide from the immune system so they can continue to grow and form tumors. Some newer approaches to immunotherapy help the immune system recognize and kill these cancer cells, making the therapy an effective treatment for many types of cancer.

What Is Immunotherapy?

The National Cancer Institute defines immunotherapy as “a type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases.” Examples of immunotherapies include vaccines and antibodies used to treat cancer.

Immunotherapy used to treat lung cancer mainly consists of monoclonal antibodies, which are bioengineered proteins (proteins made in a lab). These antibodies are slightly different from antibodies found naturally in the body because they only bind to one specific part of a protein (known as an antigen). This feature makes them helpful for targeting cancer while avoiding healthy cells.

Immune Checkpoint Inhibitors

In the human body, it is important that the immune system is able to regulate itself to prevent inflammation and autoimmunity, in which the body attacks itself. This regulation is done through a system of “checkpoint proteins” that are found on different immune cells. Checkpoint proteins act like switches to turn an immune response on or off.

One immune checkpoint system is known as the PD-1/PD-L1 checkpoint. The protein PD-1 is found on the surface of a specialized group of immune cells known as T cells. The protein PD-L1 is normally found on other immune cells, but tumor cells can also express it on their surface. When PD-1 and PD-L1 interact with one another, the T cell is shut down and does not generate an immune response. This interaction is important in cancer because tumor cells that express PD-L1 can stop the immune system from attacking them.

Monoclonal antibodies used to treat lung cancer are known as immune checkpoint inhibitors (ICI). These drugs interact with PD-1 or PD-L1 to inhibit them, or prevent them from binding to each other. This keeps the T cells and immune system activated. As a result, the immune system attacks the tumor cells and the tumors shrink over time.

Types of PD-1 and PD-L1 Inhibitors

The U.S. Food and Drug Administration (FDA) has approved four PD-1 inhibitors to treat advanced non-small cell lung cancer (NSCLC):

• Pembrolizumab (Keytruda)
• Cemiplimab (Libtayo)
• Nivolumab (Opdivo)
• Atezolizumab (Tecentriq)

The FDA has also approved a PD-L1 inhibitor for treating both advanced small cell lung cancer (SCLC) and NSCLC: durvalumab (Imfinzi).

When Are PD-1 and PD-L1 Inhibitors Used?

Immune checkpoint inhibitors can be used to treat different cases of NSCLC and SCLC. Lab tests (such as biopsies) may be done before treatment to see how much PD-1 or PD-L1 is being expressed by T cells in and around the tumor and tumor cells themselves. Some examples of treatments include the following:

• Keytruda and Libtayo are given to people with stage 3 NSCLC who cannot have radiation therapy or chemotherapy.
• Keytruda, Libtayo, or Tecentriq are given as a first-line treatment (in combination with chemotherapy) to some people with advanced NSCLC.
• Keytruda, Opdivo, and Tecentriq are used in certain cases of advanced NSCLC that have relapsed (begun growing again) after treatment with chemotherapy or other drugs. They can also be used as single agents if a person’s PDL-1 levels are sufficiently high.
• Imfinzi is used to treat stage 3 NSCLC that cannot be removed with surgery and that has not progressed after treatment with chemotherapy and radiation. It is used for consolidation therapy (keeping the cancer from getting worse over time).
• Imfinzi and Tecentriq are used as first-line treatments for advanced SCLC in combination with platinum-based chemotherapy — such as cisplatin or carboplatin — and etoposide.

CTLA-4 Inhibitors

CTLA-4 is another checkpoint used by the immune system to control the activity of T cells. Ipilimumab (Yervoy) is the only FDA-approved CTLA-4 inhibitor that treats advanced NSCLC. It is used in combination with Opdivo and chemotherapy as a first-line treatment for those with advanced NSCLC.

Side Effects of Immunotherapy

Immunotherapy and ICI work to activate your immune system, and they can cause many common side effects that are similar to flu-like symptoms. Side effects include:

• Fever
• Nausea
• Fatigue
• Loss of appetite
• Itching or skin rash
• Joint pain
• Diarrhea
• Headache
• High or low blood pressure

Infusion Reactions

Immunotherapy drugs are typically given by injection into a vein (intravenously), which can lead to an infusion reaction. Infusion reactions look and feel similar to an allergic reaction and can include symptoms such as:

• Fever
• Chills
• Itchy skin
• Flushing in the face
• Rash
• Wheezing or trouble breathing
• Dizziness

If you begin experiencing any of these symptoms during an infusion, let your doctor or nurse know immediately.

Autoimmune Reactions

In some cases, immunotherapy can over-activate the immune system and cause it to start attacking healthy tissues in other parts of the body, including the intestines, liver, lungs, kidneys, and other organs. If you begin having autoimmune reactions, your doctor may adjust your medication or prescribe other medications to address the reaction.

Talk With Others Who Understand

MyLungCancerTeam is the social network for people with lung cancer and their loved ones. On MyLungCancerTeam, more than 6,000 members come together to ask questions, give advice, and share their stories with others who understand life with lung cancer.

Are you taking immunotherapy for lung cancer? Share your experience in the comments below, or start a conversation by posting on MyLungCancerTeam.