Immunotherapy for Skin Cancer: How It Works

Your immune system helps protect your body from skin cancer, but sometimes cancer cells can “hide” from the immune system and keep growing. Immunotherapy helps your immune cells find and fight these cancer cells. Although immunotherapy doesn’t work for everyone, it has become an important treatment option for advanced skin cancer.

In this article, we’ll explain how immunotherapy is used to treat nonmelanoma skin cancer. We’ll cover how these treatments work, possible side effects, and when immunotherapy may be part of a skin cancer treatment plan.

What Types of Immunotherapy Treat Skin Cancer?

Your immune system is always checking your body for cancer cells. Special immune cells called T cells help find and destroy cancer cells. Many cancer immunotherapies work by helping T cells better recognize and attack cancer.

Some types of immunotherapy use modified viruses that target and kill cancer cells. These treatments can also help activate the immune system.

Several immunotherapies are used to treat melanoma skin cancer. Some are also approved for nonmelanoma skin cancers, including:

• Cutaneous squamous cell carcinoma (SCC)
• Basal cell carcinoma (BCC)
• Merkel cell carcinoma (MCC)

PD-1/PD-L1 Inhibitors

Your immune system uses specialized “checkpoint” proteins to keep it from attacking healthy cells. Some skin cancer cells hijack these proteins to hide from the immune system and avoid being destroyed.

One checkpoint protein on T cells is called programmed cell death protein 1 (PD-1). PD-1 interacts with a related protein called programmed death-ligand 1 (PD-L1), which can be found on some cancer cells. When PD-1 and PD-L1 connect, the immune system may stop attacking the cancer.

Immune checkpoint inhibitors (ICIs) are drugs that block these checkpoint proteins. Some target proteins on cancer cells, while others target proteins on immune cells. Blocking these proteins helps the immune system recognize and destroy cancer cells.

The U.S. Food and Drug Administration (FDA) has approved several ICIs for nonmelanoma skin cancer. Examples include:

• PD-1 inhibitors — Cemiplimab (Libtayo) and pembrolizumab (Keytruda)
• PD-L1 inhibitors — Avelumab (Bavencio) and cosibelimab (Unloxcyt)

ICIs are also FDA-approved for melanoma skin cancer. Options for metastatic melanoma — skin cancer that has spread to other parts of the body — include:

• Atezolizumab (Tecentriq)
• Nivolumab (Opdivo)
• Nivolumab and relatlimab-rmbw (Opdualag)
• Pembrolizumab

CTLA-4 Inhibitors

Cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors are another type of ICI. They work by blocking the CTLA-4 protein on T cells, helping the immune system attack cancer cells.

The CTLA-4 inhibitor ipilimumab (Yervoy) is FDA-approved to treat melanoma. Doctors usually combine ipilimumab with a PD-1 inhibitor such as nivolumab to improve treatment response.

Oncolytic Virus Therapy

Some immunotherapies use viruses that are modified to target cancer cells. These treatments, called oncolytic virus therapies, infect and kill cancer cells while mostly leaving healthy cells unharmed. Oncolytic viruses can also help the immune system find and destroy any remaining cancer cells.

The FDA has approved talimogene laherparepvec (Imlygic), also called T-VEC, to treat melanoma. T-VEC is injected directly into tumors. Common side effects of this oncolytic virus include pain at the injection site and flu-like symptoms.

When Is Immunotherapy Used To Treat Skin Cancer?

Immunotherapy can help treat advanced skin cancers. It may be used alone or combined with other treatments. The type of immunotherapy your doctor recommends depends on the type of skin cancer you have.

Some skin cancers are considered advanced because they’ve spread to other parts of the body. Others are advanced because they’ve grown deep into nearby tissue. Immunotherapy is often used when skin cancer can’t be removed with surgery, has come back after treatment, has spread, or can’t be controlled with surgery or radiation therapy.

Advanced squamous cell carcinoma may be treated with:

• Cemiplimab
• Cosibelimab
• Pembrolizumab

Doctors sometimes use cemiplimab after surgery and radiation therapy for SCC. This is called adjuvant therapy. Adjuvant treatments help destroy any cancer cells left behind after other treatments and may help lower the risk of SCC coming back.

Cemiplimab may also help treat advanced BCC that still grows after treatment with other medications. This immunotherapy is often used after trying drugs such as:

• Sonidegib (Odomzo)
• Vismodegib (Erivedge)

Avelumab and pembrolizumab can treat Merkel cell carcinoma, which is a rare skin cancer. They’re usually used for stage 3 or 4 cancers that can’t be cured with surgery. Doctors sometimes give immunotherapy with chemotherapy for better results.

What Are The Side Effects of Immunotherapy for Skin Cancer?

Immunotherapy is a body-wide, or systemic, treatment. Possible side effects include:

• Extreme tiredness
• Nausea and loss of appetite
• Diarrhea or constipation
• Skin rashes
• Bone and joint pain and inflammation

Some side effects are mild and can be managed at home. However, immunotherapy can also cause serious side effects in some people. Contact your cancer care team right away if your symptoms are severe, new, or getting worse.

Tips for managing side effects at home include:

• Taking short naps and getting light exercise to help with fatigue
• Protecting your skin with sunscreen and clothing
• Applying lotion to treat rashes
• Drinking plenty of water and limiting spicy and high-fat foods to help with an upset stomach

Autoimmune Reactions

Because immunotherapy affects the immune system, some people develop autoimmune reactions. This means the immune system attacks healthy cells and tissues. Immunotherapy can cause this by blocking signals that usually help keep immune cells from attacking healthy parts of the body.

Doctors often treat these reactions with steroids to calm the immune system. In more serious cases, they may need to reduce the dose, pause or stop treatment, or use other medications.

Infusion Reactions

Many immunotherapies are given as an intravenous (IV) infusion. Your care team will monitor you closely during treatment for possible side effects. Infusion nurses are trained to recognize and treat infusion reactions.

Infusion reactions can look similar to allergic reactions. Be sure to let your healthcare team know if you have:

• Itching, hives, or skin rashes
• Nausea or vomiting
• Lightheadedness or dizziness
• Wheezing or trouble breathing
• Fever and chills
• Flushing of the face and neck
• Fast heartbeat

Some people take medications before their infusions to help prevent reactions. These premedications may include:

• Steroids such as dexamethasone or prednisone to reduce inflammation
• Antihistamines such as diphenhydramine to prevent allergic reactions
• Fever-reducing medications such as acetaminophen

Many of these medications can also treat an infusion reaction. Severe allergic reactions, including anaphylaxis, are treated with epinephrine.

How Effective Is Immunotherapy for Treating Skin Cancer?

Immunotherapy offers another treatment option for people with advanced skin cancer. Researchers study these treatments in clinical trials, which are large studies that test how well new treatments work and how safe they are.

Many clinical trials have looked at how effective immunotherapy is for skin cancer. These treatments are most often used for advanced cancers that have spread or can’t be treated with surgery or radiation therapy.

How well immunotherapy works varies a lot based on the type of skin cancer, how advanced it is, and which drug is used. Some people respond very well, while others do not respond at all. Your doctor will watch you closely to see how well the treatment is working.

Immunotherapy doesn’t work for everyone. Studies show that fewer than 50 percent of melanomas treated with an ICI respond to treatment. Possible reasons include the following:

• There may not be enough T cells to fight the cancer.
• The immune system may not have enough specialized immune cells to activate T cells.
• The cancer cells may not have enough mutations (DNA changes) for the immune system to recognize them as harmful.

Some people also develop resistance to immunotherapy, meaning the treatment stops working over time. One small study found that 31 percent of people with MCC responded after switching to a different immunotherapy drug.

What New Treatments Are Being Studied for Skin Cancer?

Researchers are always studying new ways to treat skin cancer. Many clinical trials are testing combinations of existing treatments, while others are studying new drugs that are still being developed.

For example, one study is testing whether injecting cemiplimab directly into SCC tumors works better for some people. Usually, cemiplimab is given as an IV infusion into the bloodstream.

Immunotherapy is already helping some people with advanced skin cancer live longer. As researchers learn more about these treatments, they hope to improve results even further.

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