Immunotherapy
Side Effects

Learn what side effects can happen from immunotherapy, what to watch for, and how they are managed

What Are Immunotherapy Side Effects?

Immunotherapy helps your immune system recognize and attack cancer cells. Sometimes, that immune response can also affect healthy organs or tissues. These are collectively called immune-related side effects, or immune-related adverse events (irAEs).

Immunotherapy side effects can affect almost any part of your body. Many side effects are mild to moderate, such as fatigue, rash, itching, or diarrhea, and can be managed effectively when they are recognized early. Others can be serious, including inflammation of the lungs, intestines, liver, heart, and some endocrine conditions, which may require long-term care.

Immunotherapy side effects can be different from chemotherapy or radiation side effects because these treatments work in different ways. Chemotherapy and radiation damage or kill fast-growing cells — both cancer cells and healthy cells — which can cause side effects such as fatigue, hair loss, nausea, or low blood cell counts. Immunotherapy side effects happen because the immune system becomes overactive and attacks healthy parts of the body.

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How Common Are Immunotherapy Side Effects?

Side effects are common with some types of immunotherapy. But, the likelihood varies depending on the type of immunotherapy, whether it is given alone or in combination with other treatments, the cancer being treated, and individual patient factors.

Most of what is known about immunotherapy side effects comes from patients treated with immune checkpoint inhibitors (ICIs). Many patients have some type of immune-related side effect, but most are mild to moderate. Severe side effects are less common and are usually managed by pausing treatment and giving medicines that suppress, or calm, your immune system.

Side effects are more likely when immunotherapy is combined with another treatment. They are generally less common with a single ICI, more common when two ICIs are used together, and most common when an ICI is combined with targeted therapies. When combined with a targeted therapy, most side effects come from the targeted therapy rather than the immunotherapy.

Chimeric antigen receptor (CAR) T-cell immunotherapy has a different pattern of side effects. Many patients have cytokine release syndrome (CRS), an immune reaction that can cause high fever, low blood pressure, or difficulty breathing, although most cases are mild to moderate. Some patients also experience a neurological side effect called immune effector cell-associated neurotoxicity syndrome (ICANS).

Your health care team is the best source of information about which side effects are most likely with your specific treatment. Later on this page, you can learn more about possible side effects by immunotherapy type.

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When Can Immunotherapy Side Effects Appear?

Immunotherapy side effects can appear days, weeks, or even months after treatment starts. They can also happen after treatment ends, sometimes more than a year later. This is different from chemotherapy side effects, which typically begin soon after each dose.

*The most common long-lasting side effects are endocrine conditions, such as hypothyroidism, adrenal insufficiency, or type 1 diabetes. These may require lifelong hormone replacement or insulin. Other long-lasting side effects, such as vitiligo (loss of skin pigment) or chronic inflammatory arthritis, are less common.

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How Are Immunotherapy Side Effects Managed?

Many immunotherapy side effects can be effectively managed when they are reported early. Your health care team may monitor symptoms, pause treatment, prescribe medicines, or refer you to a specialist depending on which part of your body is affected and how severe your symptoms are.

Some mild side effects may only need monitoring or supportive care. For moderate or severe side effects, your doctor may pause immunotherapy and prescribe medicines to suppress your immune system, such as corticosteroids.

If side effects do not improve with corticosteroids, your doctor may use other medicines that target specific parts of your immune system, such as infliximab (Remicade®), vedolizumab (Entyvio®), mycophenolate mofetil (CellCept®), tocilizumab (Actemra®), or rituximab (Rituxan®). Some serious side effects may require hospitalization.

Side effects related to CAR T-cell therapy are managed differently because this treatment can cause CRS and neurological side effects. Because of these risks, CAR T-cell therapy is given at specialized cancer centers with intensive monitoring during the first weeks after treatment, so any side effects can be recognized and managed quickly. CRS is most often treated with tocilizumab and supportive care.

What You Can Do

You can help your health care team identify and manage side effects by:

• Tracking symptoms in a journal or app, including when they started and how severe they are
• Reporting any new or worsening symptoms promptly, even if they seem minor
• Carrying a wallet card or written note that says you are receiving immunotherapy
• Staying hydrated and asking your doctor about nutrition, gentle activity, and sleep
• Using gentle skin care, broad-spectrum sunscreen and avoiding harsh products if skin reactions develop
• Talking to your health care team about which over-the-counter medications, supplements, or vaccinations you can take

Even minor symptoms can be early signs of a more serious side effect. The earlier a problem is identified, the more likely it can be managed without disrupting treatment.

How Doctors Grade Side Effects

Doctors often describe side effects using a grading system developed by the U.S. National Cancer Institute, called the Common Terminology Criteria for Adverse Events. This grading system helps health care teams decide how to manage side effects and whether to continue, pause, or stop treatment.

Talk with your doctor about how grading may guide decisions in your specific treatment plan.

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Do Side Effects Mean Immunotherapy Is Working?

Some studies suggest that patients who experience certain mild side effects, particularly skin changes such as vitiligo or mild rash, may be more likely to respond to immunotherapy. However, the correlation is not consistent across all cancers and treatment types.

Many people benefit from immunotherapy without experiencing any noticeable side effects. Others may have side effects even if the treatment does not work as hoped.

The most reliable way to know whether immunotherapy is working is through imaging scans, lab tests, physical exams, and other assessments recommended by your doctor.

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What Side Effects Can Different Types of Immunotherapy Cause?

The sections above cover general information about immunotherapy side effects. This section provides more detail about side effects linked to specific types of immunotherapy. Your health care team can tell you which category your treatment falls into and which side effects are most important for you to watch for.

Immune Checkpoint Inhibitors (ICIs)

ICIs release the “brakes” on your immune system, allowing it to better recognize and attack cancer. Most side effects from ICIs are mild to moderate, but some can become serious if they are not treated early.

Possible side effects include:

• Skin symptoms: Rash, itching, or vitiligo (7–18% of patients)
• Digestive symptoms: Moderate to severe diarrhea or colitis, particularly with CTLA-4 inhibitors
• Hormone-related symptoms: Hypothyroidism or hyperthyroidism are most common; less commonly, hypophysitis (pituitary inflammation), adrenal insufficiency, or type 1 diabetes (10% of patients)
• Pneumonitis: Cough, chest pain, or shortness of breath caused by lung inflammation (3% of patients)
• Liver symptoms: Abnormal liver tests or liver inflammation (1–3% of patients on a single therapy and 20% of patients on a combination treatment) 
• Inflammation affecting the heart, brain, nerves, or muscles: Rare but potentially serious side effects, including myocarditis, encephalitis, or myasthenia-like syndromes

Cell & Gene Therapy

Cell and gene therapies, such as CAR T-cell therapy, use immune cells that are collected from a patient or that are engineered in the laboratory and infused into a patient. Side effects from cell and gene therapies can be more intense and require specialized monitoring.

Possible side effects include:

• Cytokine release syndrome (CRS): An immune reaction that can cause high fever, low blood pressure, or difficulty breathing (up to 90% of CAR T-cell therapy patients)
• Immune effector cell-associated neurotoxicity syndrome (ICANS): Confusion, difficulty speaking, tremors, or seizures (25–30% of CAR T-cell therapy patients)
• Infections: A higher risk of infections, due to suppression of normal immune cell activity, particularly in the months following treatment
• B-cell aplasia and low antibody levels: Common side effects after CD19-directed CAR T-cell therapy and may require immunoglobulin replacement
• Hemophagocytic lymphohistiocytosis (HLH): A rare but serious inflammatory complication that requires urgent care 

Targeted Antibodies

Targeted antibodies bind specific markers on cancer cells or immune cells. There are many types of targeted antibodies, including monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies. Their side effects are often similar to those of other cancer treatments that are given by IV (intravenous).

Possible side effects include:

• Infusion reactions: Fever, chills, low blood pressure, or shortness of breath during or shortly after infusion
• Skin reactions: Rash or itching
• Cardiovascular effects: High blood pressure or, with some treatments, heart-related complications
• Digestive symptoms: Nausea or diarrhea
• CRS or neurological symptoms: Possible with some bispecific antibodies, similar to CAR T-cell therapy side effects

Cancer Vaccines

Cancer vaccines include therapeutic vaccines designed to help your immune system recognize cancer and preventive vaccines, which help protect against cancer. Most side effects from cancer vaccines are mild and temporary.

Possible side effects include:

• Local reactions: Pain, redness, swelling, or itching at the injection site
• Flu-like symptoms: Fever, chills, fatigue, headache, or muscle aches, usually short-lived

Oncolytic Virus Therapy

Oncolytic virus therapy uses modified viruses designed to infect and destroy cancer cells while also helping activate your immune system. Your health care team will provide instructions to reduce the risk of spreading the virus to close contacts.

Possible side effects include:

• Injection-site reactions: Pain, redness, swelling, or wound complications
• Flu-like symptoms: Fever, chills, fatigue, or muscle aches
• Skin infections: Cellulitis, which is a bacterial skin infection, or other local reactions are less common

Cytokines

Cytokines are proteins that help immune cells communicate. The cytokine treatments interferon-alpha (IF-α) and interleukin-2 (IL-2) were among the first immunotherapies approved. However, they are used less often today because they can have significant side effects and newer immunotherapies have become standard options for many cancers.

Possible side effects include:

• Flu-like symptoms: Fever, chills, fatigue, or body aches
• Cardiovascular symptoms: Low blood pressure or fluid retention, especially with high doses of IL-2
• Mood and cognitive effects: Depression or difficulty concentrating, especially with IF-α

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Are Researchers Studying Immunotherapy Side Effects?

Yes. Reducing, predicting, and treating immunotherapy side effects is a major focus of current research. Researchers are studying ways to:

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How Is CRI Advancing Research on Immunotherapy Side Effects?

Reducing the burden of side effects is essential to making immunotherapy safer and more widely accessible. The Cancer Research Institute (CRI) supports research aimed at understanding why side effects happen, predicting who may be most at risk, and developing better ways to prevent and treat them.

CRI-funded investigators are studying immunotherapy side effects from several angles, including:

Understanding why side effects happen

CRI also supports research tools and data resources that help scientists study immunotherapy side effects. For example, the CRI iAtlas, developed in partnership with Sage Bionetworks and the Institute for Systems Biology, is an open online database that helps researchers worldwide study large-scale immunological datasets to better understand patterns of patient response and toxicity.