Your gift is 100% tax deductible.
Immunotherapy for Melanoma Skin Cancer
Immunotherapies are treatments to help a person’s own immune system recognize and destroy cancer cells more effectively. Several types of immunotherapy can be used to treat melanoma.
Immune checkpoint inhibitors
Just as it’s important that immune cells in the body get activated to fight infections, it’s also important that they turn off when they are no longer needed. Checkpoint proteins act as brakes to slow down immune attacks.
Cancer cells sometimes use these checkpoints to keep from being attacked by the immune system.
Drugs that target these checkpoint proteins, called checkpoint inhibitors, can help restore the immune response against the cancer cells.
Pembrolizumab (Keytruda, Keytruda Qlex) and nivolumab (Opdivo, Opdivo Qvantig) are drugs that target PD-1, a checkpoint protein on immune cells called T cells. By blocking PD-1, these drugs boost the immune response against melanoma cells.
These drugs can be used:
- To treat melanomas that can’t be removed by surgery or that have spread to other parts of the body.
- As adjuvant treatment (after surgery) for certain stage II, III, or IV melanomas to try to lower the risk of the cancer coming back.
- As neoadjuvant treatment (before surgery) for certain stage III or IV melanomas to try to shrink tumors and make them easier to remove.
These drugs are given either as an IV (intravenous) infusion or as an injection under the skin, typically every 2 to 6 weeks, depending on the drug and why it’s being given.
Atezolizumab (Tecentriq, Tecentriq Hybreza) is a drug that targets PD-L1, a checkpoint protein related to PD-1 that is found on some tumor cells and immune cells. Blocking this protein can help boost the immune response against melanoma cells.
In people with melanomas that have a BRAF gene change, this drug can be used along with the targeted drugs cobimetinib and vemurafenib when the cancer can’t be removed by surgery or has spread to other parts of the body.
This drug can be given as an IV infusion, typically every 2 to 4 weeks, or as an injection under the skin over several minutes, typically once every 3 weeks.
Ipilimumab (Yervoy) blocks CTLA-4, another checkpoint protein on T cells.
This drug can be used to treat melanomas that can’t be removed by surgery or that have spread to other parts of the body. It might also be used for less advanced melanomas, either before surgery as neoadjuvant treatment or after surgery as adjuvant treatment.
This drug is typically used along with a PD-1 inhibitor, most often nivolumab. This increases the chance of shrinking the tumors slightly more than a PD-1 inhibitor alone, but it can also increase the risk of side effects. Ipilimumab might also be used alone if a PD-1 inhibitor is no longer working.
This drug is given as an IV infusion, usually once every 3 weeks for 4 treatments, although it might be given for longer when used after surgery.
Relatlimab targets LAG-3, another checkpoint protein on certain immune cells that normally helps keep the immune system in check.
This drug is given along with the PD-1 inhibitor nivolumab in a combination known as Opdualag. It can be used to treat melanomas that can’t be removed by surgery or that have spread to other parts of the body.
It might also be an option before surgery as neoadjuvant treatment for some melanomas.
This drug is given as an IV infusion, typically once every 4 weeks.
Possible side effects
It’s very important to report any new side effects during or after treatment with any of these drugs to your healthcare team right away. If serious side effects occur, you might need to stop treatment and take medicines to suppress your immune system.
Common side effects
Some of the more common side effects of these drugs include:
- Fatigue
- Cough
- Nausea
- Skin rash
- Poor appetite
- Joint pain
- Diarrhea
Less common but serious side effects
Other, more serious side effects occur less often.
Infusion reactions: Some people might have an infusion reaction while getting these drugs. This is like an allergic reaction and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell a healthcare provider right away if you have any of these symptoms while getting these drugs.
Immune-related adverse events (irAEs): These drugs remove one of the safeguards on the body’s immune system. Sometimes this causes the immune system to attack other parts of the body, such as the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.
Some side effects from this type of autoimmune reaction might be mild, but others can be serious or even life threatening. Some might even last for years and require long-term follow-up and treatment.
Interleukin-2 (IL-2)
Interleukin-2 is a protein that can boost the immune system in a general way. Lab-made versions of IL-2, such as aldesleukin, are sometimes used to treat melanoma.
Intralesional therapy
Melanomas that have reached the nearby lymph nodes are more likely to come back in another part of the body, even if all of the cancer is thought to have been removed. IL-2 can sometimes be injected into the tumors, known as intralesional therapy, to help lower this risk.
For advanced melanomas
IL-2 in high doses can sometimes shrink advanced melanomas when used alone. It is not used as much now as it was in the past, because the immune checkpoint inhibitors are more likely to help and tend to have fewer side effects. But IL-2 might be an option if these drugs are no longer working.
When treating advanced melanoma, IL-2 is given as IV infusions, at least at first. Some people or their caregivers might be able to learn how to give injections under the skin at home.
Possible side effects
Side effects of IL-2 can include flu-like symptoms, such as fever, chills, aches, severe tiredness, drowsiness, and low blood cell counts.
In high doses, IL-2 can cause fluid to build up in the body so that the person swells up and can feel very sick. Because of this and other possible serious side effects, high-dose IL-2 is given only in the hospital, in centers that have experience with this type of treatment.
Side effects tend to be milder when IL-2 is injected directly into the tumor.
When deciding whether to use IL-2, it’s important to consider the potential benefits and side effects of this treatment. Because of the risk of serious side effects, high-dose IL-2 is not usually a good option for people who have other serious health problems.
Tumor-infiltrating lymphocyte (TIL) therapy
TILs are immune cells called T cells that have entered (infiltrated) a tumor to attack the cancer cells. Treatments that use these cells can help shrink some melanomas. This type of treatment is also known as tumor-derived autologous T cell immunotherapy.
Lifileucel (Amtagvi) is a type of TIL therapy that can be used to treat people with advanced melanomas, after other treatments have been tried.
This treatment has several steps:
- The melanoma tumor is removed with surgery and sent to a lab, where the TILs are separated out and then multiplied over a few weeks.
- Before getting the TIL treatment, a person gets chemotherapy for about a week. This lowers their number of immune cells and gives the TILs space to work.
- The TILs are given to the person as an IV infusion in a hospital, along with IL-2 to boost their function.
- Once in the body, the TILs seek out and attack the melanoma cells.
Possible side effects
This treatment can cause serious or even life-threatening side effects, so it needs to be given in a hospital. Serious side effects can include:
- Very low blood cell counts, which can increase the risk of serious bleeding and infections
- Internal bleeding
- Serious infections
- Heart problems
- Lung problems
- Kidney problems
- Infusion reactions
Other side effects are also possible, including fever, chills, feeling very tired, skin rash, low blood pressure, and diarrhea.
Oncolytic virus therapy
Some viruses can be altered in a lab so that they infect and kill mainly cancer cells. These are known as oncolytic viruses. Along with killing the cells directly, the viruses can also alert the immune system to attack the cancer cells.
Talimogene laherparepvec (Imlygic), also known as T-VEC, is an oncolytic virus that can be used to treat melanomas in the skin or lymph nodes that come back after surgery and can’t be removed.
The virus is injected directly into the tumors, typically every 2 weeks. This treatment can sometimes shrink these tumors, and it might also shrink tumors in other parts of the body.
The most common side effects include flu-like symptoms and pain and redness at the injection site.
Vusolimogene oderparepvec (Tudriqev), formerly known as RP1, is an oncolytic virus that can be used to treat advanced melanomas that are no longer responding to a PD-1 checkpoint inhibitor (see above).
This virus is injected directly into tumors, typically every 2 weeks for 8 doses. It is given along with the checkpoint inhibitor nivolumab to help boost the immune response against the cancer cells.
Side effects can include flu-like symptoms, nausea and vomiting, diarrhea or constipation, rash, loss of appetite, belly pain, shortness of breath, bleeding, fluid retention, and pain and redness at the injection site.
Imiquimod cream
Imiquimod (Zyclara) is a topical drug that is put on the skin as a cream. It causes a local immune response against skin cancer cells.
For very early (stage 0) melanomas in sensitive areas on the face, some doctors might use imiquimod if surgery isn’t able to remove all of the tumor.
Imiquimod might also be an option to treat some melanomas that have spread along the skin, especially if surgery can’t be done.
The cream is usually applied 2 to 5 times a week for around 3 months.
Some people have serious skin reactions to this drug, and some might develop flu-like symptoms during treatment.
More information about immunotherapy
To learn more about how drugs that work on the immune system are used to treat cancer, see Cancer Immunotherapy.
To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.
- Written by
- References
Developed by the American Cancer Society medical and editorial content team with medical review and contribution by the American Society of Clinical Oncology (ASCO).
Goodman RS, Lawless A, Woodford R, et al. Extended Follow-Up of Chronic Immune-Related Adverse Events Following Adjuvant Anti–PD-1 Therapy for High-Risk Resected Melanoma. JAMA Netw Open. 2023;6(8):e2327145. doi:10.1001/jamanetworkopen.2023.27145
Mitchell TC, Karakousis G, Schuchter L. Chapter 66: Melanoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.
National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology. Melanoma: Cutaneous. Version 2.2026. Accessed at https://www.nccn.org on May 12, 2026.
Seth R, Agarwala SS, Messersmith H, et al. Systemic Therapy for Melanoma: ASCO Guideline Update. J Clin Oncol. 2023;41:4794-4820.
Sosman JA. Adjuvant and neoadjuvant therapy for cutaneous melanoma. UpToDate. 2026. Accessed at https://www.uptodate.com/contents/adjuvant-and-neoadjuvant-therapy-for-cutaneous-melanoma on May 12, 2026.
Sosman JA. Interleukin-2 and experimental immunotherapy approaches for advanced melanoma. UpToDate. 2026. Accessed at https://www.uptodate.com/contents/interleukin-2-and-experimental-immunotherapy-approaches-for-advanced-melanoma on May 12, 2026.
Sosman JA. Overview of the management of advanced cutaneous melanoma. UpToDate. 2026. Accessed at https://www.uptodate.com/contents/overview-of-the-management-of-advanced-cutaneous-melanoma on May 12, 2026.
Sosman JA. Systemic treatment of metastatic melanoma lacking a BRAF mutation. UpToDate. 2026. Accessed at https://www.uptodate.com/contents/systemic-treatment-of-metastatic-melanoma-lacking-a-braf-mutation on May 12, 2026.
Last Revised: August 12, 2026
American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy.
American Cancer Society Emails
Sign up to stay up-to-date with news, valuable information, and ways to get involved with the American Cancer Society.
