Colorectal Cancer Immunotherapy: Identifying Patients Who Benefit from MSI-High Tumors

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• Immunotherapy in Colorectal Cancer
• The Role of MSI Status
• How Checkpoint Inhibitors Work
• Current Treatment Landscape
• Future of Colon Cancer Immunotherapy
• Full Transcript

Immunotherapy in Colorectal Cancer

Immunotherapy represents a revolutionary approach to cancer treatment. Dr. Hans-Joachim Schmoll, MD, describes it as letting the body's own immune cells attack tumor cells. This method has shown remarkable success in other cancers like melanoma and kidney cancer.

In colorectal cancer, however, immunotherapy's effectiveness is currently limited. Dr. Hans-Joachim Schmoll, MD, notes that it works as a very good last-line treatment and is now moving into first-line therapy for some cancers. The central challenge in colorectal cancer is selecting the correct patients who will respond.

The Role of MSI Status

A patient's microsatellite instability (MSI) status is the critical biomarker for immunotherapy response. Dr. Hans-Joachim Schmoll, MD, explains that MSI-positive tumors have a particularly high mutation rate.

This high mutation load inside the tumor attracts many immune T-cells. These tumors are sometimes called "hot" tumors because they are already infiltrated by the immune system. This environment is primed for a response to immunotherapy drugs.

How Checkpoint Inhibitors Work

Immune checkpoint inhibitors are antibody medications that activate the patient's T-cells. Dr. Schmoll clarifies that these drugs work by blocking proteins that prevent T-cells from killing cancer cells. Effectively, they take the "brakes" off the immune system.

Common checkpoint inhibitors include pembrolizumab (Keytruda), ipilimumab (Yervoy), and nivolumab (Opdivo). When these medications are given to patients with MSI-high colorectal cancer, the activated T-cells can effectively kill the tumor cells and cancer stem cells.

Current Treatment Landscape

The current reality is that immunotherapy benefits a small, specific subgroup. Dr. Hans-Joachim Schmoll, MD, states that only 5% to 15% of all colorectal cancer patients have MSI-high tumors. For this select group, immune checkpoint inhibitors are very active and can be highly effective.

Conversely, for the vast majority—85% to 95%—of colorectal cancer patients, these immunotherapies show no efficacy. This stark difference underscores the absolute necessity of biomarker testing before considering this treatment avenue.

Future of Colon Cancer Immunotherapy

Research is intensely focused on expanding the benefits of immunotherapy. Dr. Schmoll expresses confidence that future studies will reveal how to use these powerful drugs to kill colon cancer stem cells in more patients. The goal is to make the patient's own activated immune cells the optimal means to eliminate the tumor.

Dr. Anton Titov, MD, and other oncologists await these advances. The hope is that ongoing immunotherapy research will soon deliver new strategies and combinations. These breakthroughs could significantly improve success rates for a much larger population of colorectal cancer patients.

Full Transcript

Dr. Anton Titov, MD: Colon cancer immunotherapy successfully treats 5% to 10% of patients. How do we select the correct patients for colorectal cancer immunotherapy? What are the key factors in cancer immunotherapy of colon cancer and rectal cancer?

There is another option to kill cancer stem cells. It is probably more helpful and a very recent method: immunotherapy. Immunotherapy is surprisingly active in other tumors, like kidney cancer or melanoma. This is real immunotherapy. It means we let immune cells attack the tumor cells, even when the body's own immune system was not working normally. Otherwise, a tumor would not grow.

Dr. Hans-Joachim Schmoll, MD: T-cell checkpoint inhibitors can activate immune T-cells. Such toxic T-cells can kill the tumor. Immunotherapy works in many tumor types. It is a very good last-line treatment, and now it is going to first-line therapy. But in colorectal cancer, immunotherapy doesn't work very well at the moment.

We think the key is to select a specific subgroup of colon cancer patients, about 5 to 10% of patients. It is important to let the immune cells do their work in the tumor cells and colon cancer stem cells. I'm sure in a few years, research will show how to use immunotherapy to kill colon cancer stem cells. But this is the optimal means to eliminate the tumor cells, just by the activated normal human immune cells.

Dr. Anton Titov, MD: It is also a question of selecting the right patients for immunotherapy, those 5% to 10% of colon cancer patients. Immunotherapy might work for them even at the present level of technology.

There is a specific group of colon cancer patients for whom immunotherapy may work. These tumors have the MSI characteristic. MSI is Microsatellite Instability. MSI colon cancers have a particularly high mutation rate in the tumor.

Dr. Hans-Joachim Schmoll, MD: A high mutation rate inside the tumor attracts many immune T-cells into the tumor. T-cells are activated by immune checkpoint inhibitor medications. Checkpoint inhibitors are antibodies for colorectal cancer treatment. Immune checkpoint inhibitors are very active in MSI-positive colorectal cancer. But these are only 5% to 15% of all colon cancers, depending on the patient population.

For the majority of colon cancer patients, immune checkpoint inhibitors have no efficacy. We need to do more research on immunotherapy for colon cancer. We hope that immunotherapy research will bring results for patients in the near future. Thank you.