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Melanoma is one of the deadliest forms of skin cancer. This is primarily because it spreads more aggressively than other skin cancers. Although melanoma accounts for only 1% of skin cancers, this type causes a high number of cancer-related deaths.
Because melanoma spreads so quickly, it is difficult to treat it effectively once it has spread throughout the body to lymph nodes and other organs.
Early-stage melanomas are usually treated with surgery to remove cancer cells. However, treatment for advanced cases of melanoma may include immunotherapy, a treatment that activates your immune system to fight cancer cells.
Here’s what you need to know about immunotherapy for melanoma.
How immunotherapy interacts with the immune system
Immunotherapy helps the body’s immune system better recognize and fight cancer cells. Immunotherapy can work against melanoma in different ways:
- Promote overall immune system function to destroy cancer cells
- Through targeted attacks against certain types of cancer and immune cells, so-called immune checkpoint inhibitors.
- With cell therapy, in which the patient’s tumor cells are used to activate the immune system
- Viral therapy uses viruses modified in the laboratory to attack cancer cells
Here we will take a closer look at each type of melanoma immunotherapy.
General immunotherapy
In theory, the body’s immune system can recognize and attack cancer cells to prevent them from spreading. But sometimes cancer cells can spread too quickly for the immune system to keep up, or the cells could even hide or attack the immune system. General immunotherapy uses medications that can help improve the overall function of the immune system. For example, interleukins are proteins that stimulate the immune system so that it can better recognize and attack melanoma cells. Melanoma treatment uses laboratory-made versions of the protein interleukin-2 (IL-2).
IL-2s are not used as widely as they once were because they can have serious side effects and often do not work as well as immune checkpoint inhibitors.
Immune checkpoint inhibitors
Immune checkpoint inhibitors (IPCIs) are a targeted form of immunotherapy. A key way immunotherapy works for melanoma is to “turn off” certain proteins on immune cells that prevent those cells from attacking the cancer.
In a healthy person, the immune system has built-in “checkpoints” that prevent immune cells from destroying healthy cells. Unfortunately, melanoma cells use these checkpoints against the body and can bind to them, allowing cancer to spread. Immune checkpoint inhibitors are drugs that “turn off” these specific checkpoints, allowing immune cells to recognize the melanoma and work to destroy it.
- PD-1 inhibitors: PD-1 inhibitors specifically target a cellular immune protein called PD-1. PD-1 normally prevents immune cells from destroying other cells. When PD-1 is blocked, immune cells are released to better fight melanoma cancer cells. PD-1 inhibitors are known as pembrolizumab (brand name: Keytruda) and nivolumab (brand name: Opdivo) and are administered through intravenous infusions. They can only be used for disseminated melanomas that cannot be removed surgically. They can also be used as a secondary treatment (called an immune potentiator) and as a preventive treatment to reduce the risk of cancer recurrence.
- PD-L1 inhibitors: The PD-L1 inhibitors atezolizumab (brand name: Tecentriq) work in the same way, blocking the PD-L1 protein on immune cells, which normally prevents immune cells from attacking. This type of immunotherapy can be used specifically in people suffering from metastatic melanoma with the BRAF gene mutation. It can be administered intravenously or by injection.
- CLTA-4 inhibitors: This type of checkpoint inhibitor specifically targets CTLA-4 proteins, which are found on the T cells of the immune system. When used alone, CLTA-4 inhibitors are less effective and have more serious side effects than other immunotherapy drugs, but they can be administered with PD-1 inhibitors. Ipilimumab (brand name: Yervoy) is administered through intravenous infusions.
- LAG-3 inhibitors: LAG-3 inhibitors (called relatlimab) block the checkpoint protein LAG-3. Relatlimab is usually given as an infusion in combination with a PD-1 inhibitor called nivolumab (relatlimab and nivolumab are marketed together under the brand name Opdualag).
Checkpoint inhibitors are a promising development for the treatment of melanoma. Before IPCI treatments, the average survival rate for advanced melanoma was only six months. However, survival rates are now well above the six-month rate.
Therapy with tumor infiltrating lymphocytes (TIL).
T lymphocytes are a special type of immune cell that the body uses to fight cancer. When they move toward a tumor, they are called tumor-infiltrating lymphocytes (TILs). TIL therapy is a newer cancer treatment in which TILs are removed from a tumor, grown in a laboratory, and transferred into the body through an infusion. TILs may be effective against advanced melanomas because the T cells extracted from cancer cells have “learned” to specifically recognize melanomas.
The treatment is complex and takes place in several steps in the hospital. In 2024, the US Food and Drug Administration (FDA) approved lifileucel (brand name: Amtagvi) as the first FDA-approved immunotherapy for tumor-derived T cells.
Oncolytic virotherapy
Oncolytic virotherapy involves “controlling” viruses so that they specifically attack cancer cells. Viruses are known for their ability to hide from the immune system and attack healthy cells. So scientists have found a way to harness this power by engineering viruses (called oncolytic viruses) in a laboratory so that they attack cancer cells instead.
In addition to directly destroying cancer cells, oncolytic viruses can also alert the rest of the immune system to attack cancer cells. In melanoma, talimogene laherparepvec (brand name: Imlygic), also known as T-VEC, is an oncolytic virus that can be used to try to shrink tumors that cannot be removed surgically. Currently, the main goal of oncolytic virotherapy for melanoma is to shrink tumor size, and some data show that it may help increase survival rates.
Many of the immunotherapy treatment options for melanoma can be used together, providing more opportunities for effective treatment. Additional immunotherapy options offer new hope for a very difficult type of cancer.
The best clinical treatment results are always achieved with early diagnosis. Therefore, in the fight against melanoma, it is very important to know the signs of skin cancer and undergo regular skin checks.
This educational resource was created with support from Merck.
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