Immunotherapy is a type of cancer treatment that helps the body’s immune system recognize and attack cancer cells. It has become an important treatment option for some people with colorectal cancer, particularly when the tumor has certain biomarkers.
The immune system normally protects the body from infections and other diseases. However, cancer cells can sometimes avoid detection or prevent the immune system from attacking them.
Immunotherapy works by helping the immune system:
There are several types of immunotherapy. The primary type currently used to treat colorectal cancer is called an immune checkpoint inhibitor.
Colorectal cancer immunotherapy is primarily effective for patients with specific molecular biomarkers that indicate high tumor mutation levels and immune visibility. Testing colorectal cancer for microsatellite instability (MSI) and mismatch repair (MMR) status is an important part of treatment planning.
Immune checkpoint inhibitors are most likely to benefit people whose tumors are:
These biomarkers indicate that the tumor has difficulty repairing certain types of DNA damage. As genetic errors accumulate, the cancer cells may become easier for the immune system to recognize and attack.
Tumors may instead be classified as:
Standard checkpoint inhibitors used alone have generally not been effective for most MSS or pMMR colorectal cancers. However, researchers are investigating new immune-based approaches for these tumors.
The immune system uses proteins called checkpoints to regulate immune activity and prevent immune cells from damaging healthy tissue. Colorectal cancer cells may use these checkpoints to avoid being recognized or attacked.
Checkpoint inhibitors block these signals and help restore the immune system’s ability to recognize and attack cancer cells.
Checkpoint inhibitors are approved for certain people with MSI-H or dMMR colorectal cancer. Treatment recommendations depend on factors that include:
For unresectable or metastatic MSI-H or dMMR colorectal cancer, immunotherapy may be used as an initial treatment or after other treatments, depending on the drug or drug combination. In April 2025, the FDA approved nivolumab plus ipilimumab for patients aged 12 and older with unresectable or metastatic MSI-H or dMMR colorectal cancer.
Immunotherapy is also being studied for people with earlier-stage colorectal cancer, including treatment before or after surgery. Some approaches have produced encouraging research results, but availability outside a clinical trial depends on the individual situation and current treatment guidelines.
This short video from the American Cancer Society provides answers to some of the most common questions that people with cancer have about immunotherapy.
The FDA has approved several checkpoint inhibitor drugs for colorectal cancer treatment for tumors with high microsatellite instability (MSI-H) or DNA mismatch repair deficiency (dMMR). There are also several antibody-based therapies that the FDA has approved for MSI-H/dMMR and MSS/pMMR CRC diagnoses.
Another biomarker, high tumor mutational burden (TMB-H), may affect whether pembrolizumab or a clinical trial should be considered in certain circumstances. Your healthcare team should review all biomarker results—not only MSI and MMR status—when discussing treatment options.
Drug approvals and treatment guidelines can change. Ask your healthcare team which treatments are currently approved and appropriate for your diagnosis.
A PD-1 inhibitor approved as a first-line treatment for unresectable or metastatic MSI-H or dMMR colorectal cancer.
A PD-1 inhibitor approved for certain patients age 12 and older with MSI-H or dMMR metastatic colorectal cancer, including after specified chemotherapy treatments.
A combination that targets the PD-1 and CTLA-4 pathways. It is approved for patients aged 12 and older with unresectable or metastatic MSI-H or dMMR colorectal cancer.
A PD-1 inhibitor with a tumor-agnostic accelerated approval for certain adults with recurrent or advanced dMMR solid tumors that have progressed after prior treatment and have no satisfactory alternative treatment options. This indication may include eligible colorectal cancers.
A monoclonal antibody, but it is generally classified as a targeted therapy in colorectal cancer.Bevacizumab targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced colorectal cancer, including as a first-line therapy.
A monoclonal antibody, but it is generally classified as a targeted therapy in colorectal cancer. Cetuximab targets the EGFR pathway; approved for subsets of patients with advanced, EGFR-positive colorectal cancer, including as a first-line therapy.
A monoclonal antibody, but it is generally classified as a targeted therapy in colorectal cancer. Panitumumab targets the EGFR pathway; approved for subsets of patients with advanced, EGFR-positive colorectal cancer.
A monoclonal antibody, but it is generally classified as a targeted therapy in colorectal cancer. Ramucirumab targets the VEGF/VEGFR2 pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced colorectal cancer, including as a first-line therapy.
You may receive immunotherapy in your doctor’s office or in an outpatient cancer center at a hospital.
There are different forms of immunotherapy. The most common for colorectal cancer treatment are:
Treatment may be given every few weeks. The exact schedule and length of treatment depend on:
Your care team will explain what to expect before treatment begins.
For most people with MSS or pMMR colorectal cancer, standard immune checkpoint inhibitors used alone have not produced the same benefit seen in MSI-H or dMMR tumors.
One reason is that MSS tumors may be less visible to the immune system. The environment surrounding the tumor may also make it difficult for immune cells to enter the tumor or remain active.
Researchers are studying ways to overcome these barriers, including:
These investigational approaches have not yet been proven safe and effective for most people with MSS or pMMR colorectal cancer. They are generally available only through clinical trials.
Clinical trials are evaluating new ways to use immunotherapy throughout colorectal cancer care, including:
Clinical trials may evaluate a new drug, a new treatment combination, a different treatment schedule or the use of an existing therapy in a new setting.
Asking about clinical trials early can give you and your healthcare team more time to identify studies that may fit your:
A clinical trial may not be appropriate or available for everyone. Participation is voluntary, and the study team should explain the potential benefits, risks, requirements and alternatives before you decide whether to participate.
Immunotherapy affects each person differently. Side effects can occur during treatment or after treatment has ended.
Common side effects of checkpoint inhibitors may include:
Because checkpoint inhibitors activate the immune system, they can sometimes cause immune cells to attack healthy organs and tissues. These immune-related side effects may affect the intestines, lungs, liver, skin, thyroid or other hormone-producing glands, kidneys, nervous system, heart, or other organs.
Some immune-related side effects can become serious or life-threatening if they are not treated promptly.
Side effects from specific types of immunotherapies
Each type of immunotherapy has its own set of potential side effects. Click on the types below to learn about side effects associated with each:
Tell your healthcare team promptly about any new, worsening or unusual symptoms—even if they seem minor or occur after treatment has ended.
Contact your care team right away if you experience symptoms such as:
Do not try to manage a possible immune-related side effect without speaking with your healthcare team. Early treatment can help prevent complications.
Consider asking:
Treatment decisions should be based on your complete diagnosis, biomarker results, previous treatments, health and personal treatment goals. Your healthcare team can help you understand the possible benefits and risks of each option.
There are some precautions to keep in mind when you are receiving immunotherapy since some forms are considered hazardous.
Protect yourself and others: Your care team may caution you to not let others come into contact with the drug or your body fluids while taking it, and for a period after taking it. You may be advised to wear protective gloves when you are handling the drug.
Disposal: Some drugs and their packaging will need to be disposed of in a certain way. If you are taking an oral immunotherapy drug at home, be sure to ask your care team about any special instructions for using them safely.
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