Immunotherapy for Colorectal Cancer

What is immunotherapy?  

Immunotherapy is a cancer treatment that helps the body's own immune system kill cancer cells.

What type of immunotherapy is used to treat colorectal cancer?  

There are several types of cancer immunotherapy, including immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, oncolytic virus therapy, and cancer vaccines. The immunotherapy used to treat colorectal cancer is a group of drugs called immune checkpoint inhibitors.  

The immune checkpoint inhibitors are biologic medicines, specifically monoclonal antibodies (mAbs), engineered in a laboratory to bind to specific molecules on the surface of your immune system cells. The three drugs used to treat colorectal cancer are ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda).  

How do immune checkpoint inhibitors work?  

The immune system has checkpoints that function as on-off switches. The checkpoints allow adjustment of the strength of an immune response. By turning the immune checkpoint on or off, your body can create an immune response to abnormal cells (cancer cells, bacteria, virus-infected cells, etc.) but also maintain control of the response so that it does not get so strong that it destroys healthy cells.  

T-cells, also called T-lymphocytes, are immune cells that recognize and kill cancer cells. T-cells have checkpoint receptors on their surface called CTLA-4 and PD-1. Tumor cells may make proteins that bind to the CTLA-4 and PD-1 receptors and turn off the immune checkpoints. In this way, tumor cells can suppress the immune system and avoid being destroyed. Immune checkpoint inhibitors block the tumor's ability to suppress the immune system, and turn the immune checkpoint switch back on, activating the immune system to target the cancer cells. There are two subtypes of immune checkpoint inhibitors used to treat colorectal cancer, CTLA-4 inhibitors and PD-1 inhibitors. (Two other types, PD-L1 inhibitors and LAG-3 inhibitors, are used to treat other cancer types like lung cancer and melanoma.) Ipilimumab works at the CTLA-4 checkpoint, and nivolumab and pembrolizumab work at the PD-1 checkpoint.  

How do I know if immunotherapy is a treatment option for me?

Current treatment guidelines recommend the use of immunotherapy in advanced colorectal cancer, especially metastatic colorectal cancer (mCRC).  

To find out if your cancer might be effectively treated with immunotherapy, you need to have biomarker testing. Biomarker testing is at the center of personalized medicine, an approach in which a person's tumor biomarkers are used to help in cancer diagnosis, treatment, and follow-up.  

The biomarkers that affect your immunotherapy options are all related to DNA mutations in your cancer cells.  

When cells grow and divide, there are errors that occur in DNA copying called DNA mismatch. The process of fixing these mistakes is called DNA mismatch repair (MMR). Errors that do not get repaired are mutations. Microsatellites are small, repetitive segments of genomic DNA. Mismatch repair status can be determined by looking at whether these DNA segments have few mutations or many mutations.

Microsatellite stability (MSS)

If your cells are able to fix the errors, your cancer is considered microsatellite stable (MSS). Microsatellite stability is also called proficient mismatch repair (pMMR). About 85% of colorectal cancers are MSS.    

MSS colorectal tumors do not typically respond to immune checkpoint inhibitor treatment. However, the subset of colorectal cancer patients with MSS who also have a high tumor mutational burden may have a good clinical response to immunotherapy. Tumor mutational burden (TMB) is a measurement of how many mutations there are in your tumor's genes (tumor DNA).

In addition, there are ongoing clinical trials treating MSS colon cancer and rectal cancer with drug combinations, including new immune checkpoint inhibitors alongside other targeted therapy drug and conventional chemotherapy. Talk to your oncologist about whether a clinical trial might be right for you. To learn more about clinical trials, please check out our Clinical Trial Awareness program.  

Microsatellite instability (MSI)  

If your tumor cells are unable to correct DNA mismatch errors that occur when cells grow and divide, your cancer is mismatch repair deficient. This is also called microsatellite instability (MSI) or microsatellite instability-high (MSI-H).  

If biomarker testing reveals that your colorectal cancer has microsatellite instability, you will also need genetic testing for Lynch syndrome, a hereditary cancer syndrome caused by deficient mismatch repair (dMMR).

Colon cancer and rectal cancer with MSI-High are particularly susceptible to immunotherapy, meaning colorectal cancer patients with MSI-H often have a good response to immune checkpoint inhibitor treatment. Immune checkpoint inhibitors are a first-line treatment for metastatic colorectal cancer with microsatellite instability.

For more information about biomarkers and how they can affect your treatment options, please visit knowyourbiomarker.org.

How is immunotherapy given?  

Immune checkpoint inhibitors are given by infusion into a vein. These intravenous infusions take around 30 minutes and are done as an outpatient at an infusion center, hospital outpatient department, or doctor's office. Immunotherapy may be given alone in some cases, or in combination with chemotherapy drugs or targeted therapy drugs. Sometimes two immune checkpoint inhibitors are used together.

What are the side effects of immunotherapy?  

The most common side effects of immune checkpoint inhibitors are fatigue, skin rash, diarrhea, cough, loss of appetite, and joint pain. More rarely, immune checkpoint inhibitors can cause more severe autoimmune inflammation in organs throughout the body like skin, lungs, intestines, pancreas, liver, and heart.

Talk to your oncology team about any side effects you experience.