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How immunotherapy treats melanoma skin cancer

An overview of how immunotherapies treat melanoma, with a look at subcutaneous immune checkpoint inhibitors.

An oncologist prepares an injection of a subcutaneous immunotherapy. Subcutaneous immune checkpoint inhibitors are one of several immunotherapies used in the treatment of melanoma.

Updated on June 4, 2025

Although it accounts for only 1 percent of all skin cancers, melanoma is considered the most serious type of skin cancer. The majority of skin cancer deaths are caused by melanomas. Compared to other skin cancers, melanoma grows quickly and is more likely to metastasize (spread) to other areas of the body.

Treatment for melanoma will depend on the stage of the cancer, the overall health of the person being treated, and numerous other factors.

A treatment plan for melanoma may include immunotherapy, a type of cancer treatment that helps the body’s immune system identify and eliminate cancer cells.

Immune checkpoint inhibitors

The main type of immunotherapy used in the treatment of melanoma are drugs called immune checkpoint inhibitors.

An immune checkpoint is a protein that prevents the immune system from attacking healthy cells. Immune checkpoints are found on the surface of cells throughout the body. Cancer cells can have immune checkpoints. This helps cancer cells continue to grow and spread without being attacked by the immune system.

Immune checkpoint inhibitors disable (or inhibit) immune checkpoints. This enables the immune system to recognize cancer cells for what they are—abnormal cells that need to be eliminated.

What immune checkpoints inhibitors treat melanoma?

Different immune checkpoint inhibitors act on different immune checkpoints. The immune checkpoints that are targeted in the treatment of melanoma include:

  • PD-1 (programmed death receptor-1)
  • PD-L1 (programmed death-ligand 1)
  • LAG-3 (lymphocyte activation gene 3)
  • CTLA-4 (cytotoxic T-lymphocyte-associated protein 4)

A healthcare team may order tests to look at genetic and molecular characteristics of a tumor (called biomarker testing). This can help predict how the cancer will respond to immunotherapy, and what type of immunotherapy it may respond to.

How are immune checkpoint inhibitors administered?

Most immune checkpoint inhibitors are administered with intravenous infusions, where a needle is inserted into a vein. This is typically done at an infusion center or a hospital. While infusion schedules vary depending on the specific drug being used, infusions are typically given every 2 to 6 weeks. The number of infusions a person will need will vary.

Certain immune checkpoint inhibitors can be given as subcutaneous injections. A subcutaneous injection is administered with a needle inserted into the subcutaneous layer, a layer of tissue immediately underneath the skin. These injections are typically given in the abdomen or thigh, (and specific drugs may only be injected at specific spots on the body). Subcutaneous immunotherapy drugs work the same as their intravenous counterparts, the only difference is the route of administration.

A small number of subcutaneous immunotherapy drugs are available, but more are under development. Subcutaneous administered cancer treatments are a topic of interest to medical researchers because this route of administration has the potential to make treatments like immunotherapy more accessible to more people.

Subcutaneous injections take much less time than an intravenous infusion and can also be administered at a healthcare provider's office (instead of an infusion center or hospital).

Other types of immunotherapy

Several other types of immunotherapy may be used in treating melanoma. These are typically used less often than immune checkpoint inhibitors, but they remain important options:

Cytokine therapy

Cytokines are proteins that help regulate the activity of the immune system. Infusions of a lab-made cytokine called interleukin-2 (IL-2) are used as treatments for melanoma. These infusions increase immune system activity and help the immune system attack cancer cells.

Oncolytic virus therapy

This approach uses modified viruses that can infect and destroy cancer cells while mostly avoiding healthy cells.

Tumor-infiltrating lymphocyte (TIL) therapy

This treatment involves collecting immune cells called T cells from a melanoma tumor that has been removed using surgery. T cells are capable of destroying cancer cells, but there are usually not enough T cells to destroy an entire tumor.

Copies of the collected T cells will be grown in a lab. The lab-grown cells will be used to create an infusion that contains a large number of these T cells. This infusion will be delivered into the vein of the person being treated. Because these T cells have been collected from a tumor, they should be effective at infiltrating cancer in other places throughout the body.

While this treatment can be effective, it can cause serious (and in some cases life-threatening) side effects.

Cancer vaccines

Though not as widely used as other treatments, the Bacille Calmette-Guerin (BCG) vaccine can sometimes be used. This vaccine is directly injected into a tumor to stimulate an immune response against melanoma cells.

Topical immunotherapy

There is also a topical immunotherapy that is sometimes used in early-stage melanoma or melanomas that have spread across the skin. This is a cream that has been applied directly to the skin.

Your best source of information

Like all cancer treatments, immunotherapies can cause side effects. Side effects can depend on the type of immunotherapy being used. Before starting any type of immunotherapy—or any other type of cancer treatment—talk to your healthcare provider about the potential side effects.

It's important to remember that there is no best treatment for melanoma, only the treatment that is best for a particular person at a particular time. If you have questions about a diagnosis of melanoma, immunotherapy, or other treatment options, your best source of information will be your healthcare team.

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