Immunomodulators and Their Side Effects
While other types of cancer immunotherapy act on specific parts of the immune system, immunomodulators work in broader, less targeted ways to boost the body’s immune response to cancer or certain other diseases.
What are immunomodulators?
Immunomodulator drugs (iMiDs), sometimes called biological response modifiers, are a group of drugs that target the action of certain proteins as part of the immune system’s response to kill cancer cells.
They are a broad group of medications that treat a variety of different conditions, including:
- Asthma
- Autoimmune disease
- Cancer
- Eczema
- Inflammatory bowel disease (Crohn’s disease, ulcerative colitis)
- Infection
How do immunomodulators work in treating cancer?
Immunomodulators work to either “turn up” or “turn down” certain proteins in the body. When proteins are turned up, this can lead to an increased response of the immune system. In cancer treatment, this can be helpful in allowing the immune system to work more effectively to find and destroy cancer cells.
When proteins are turned down, this can lead to a decreased response of the immune system. This can be helpful in cancer treatment by:
- Helping the body overcome the defense mechanisms cancer cells use to try and protect themselves against the immune system
- Blocking the ways cancer cells grow and divide, limiting their ability to make more cancer cells
- Reducing the immune system’s response to donated tissue or blood following a stem cell or bone marrow transplant
Other types of immunotherapy also have immunomodulatory action:
- Immune checkpoint inhibitors block checkpoint proteins that act as “off switches” in the body. This helps the immune system destroy the cancer cells
- Cytokines turn on immune cells to be more effective against cancer
- CAR T-cell therapy turns on white blood cells called T-cells so they can better kill cancer cells
How are immunomodulators given?
Depending on the type, iMiDs given for cancer are given as an infusion into a vein (IV), pills or capsules that you swallow (oral), subcutaneous injections under the skin (SQ), or cream that you apply to your skin (topical). Some can be given alone but most are used in combination with other cancer treatments, including chemotherapy or immunotherapy.
Types of immunomodulators used as immunotherapy
Thalidomide, lenalidomide, and pomalidomide
Thalidomide (Thalomid), lenalidomide (Revlimid), and pomalidomide (Pomalyst) are iMiDs used to treat multiple myeloma, sometimes in combination with corticosteroids. They are taken daily as pills, with breaks from treatment on certain days each month. Because these drugs can increase the risk of serious blood clots, they are often given along with aspirin or a blood thinner.
These drugs might cause severe birth defects when taken during pregnancy. Because of this, they have special requirements. You will need to:
- Enroll in a special program run by the drug company that makes them.
- Take steps to not become pregnant while undergoing treatment.
- Follow special handling precautions to keep them away from others.
Your doctor will talk with you more about the specific safety requirements.
Imiquimod
Imiquimod is a cream used to treat some very early-stage skin cancers (or pre-cancers), especially if they are in sensitive areas such as on the face. It stimulates a local immune response against skin cancer cells.
The cream is applied to the skin anywhere from once a day to twice a week for several months. Some people have serious skin reactions to this drug.
Side effects of immunomodulators
Side effects of iMiDs differ from person to person and depend on the type of iMID used.
Common side effects of thalidomide, lenalidomide, and pomalidomide include:
- Diarrhea or constipation
- Fatigue
- Skin rashes
- Low blood counts
- Increased risks of certain infections
- Neuropathy
- Increased risk of blood clots
Common side effects of imiquimod include:
- Redness, burning, or irritation at the treatment site
- Dryness or flakiness of the skin
- Pain
- Swelling
Your cancer care team will watch you closely during treatment and will check you often. Side effects can and should be treated as early as possible. It’s important to tell your cancer care team about any changes in how you feel or anything you notice that’s new or unusual. Tell them right away so they can treat any problems and try to keep them from getting worse.
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- 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).
American Society of Clinical Oncology. What is Immunotherapy? Accessed at cancer.net. Content is no longer available.
American Society of Clinical Oncology. Side effects of immunotherapy. Accessed at cancer.net. Content is no longer available.
Gordon RA, Jackson N, Krause T, Mangan B, Martinez AL, Tipian CC. Immunotherapy. In Olsen MM, LeFebvre KB, Walker SL, Dunphy EP, eds. Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice. 2nd ed. Pittsburgh, PA: Oncology Nursing Society; 2023:213-290.
National Cancer Institute (NCI). Immune system modulators. Updated September 24, 2019. Accessed at https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/immune-system-modulators on August 7, 2025.
Shoushtari AN, Johnson DB. Principles of cancer immunotherapy. UpToDate. 2024. Accessed at https://www.uptodate.com/contents/principles-of-cancer-immunotherapy on August 7, 2025.
Last Revised: July 7, 2025
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