Dr. Bekaii-Saab on the Role of Immunotherapy in CRC

Tanios Bekaii-Saab, MD
Published Online: Friday, Dec 23, 2016



Tanios Bekaii-Saab, MD, professor of Medicine, Mayo Clinic, discusses the role of immunotherapy in the treatment of patients with colorectal cancer (CRC).

When looking at patients with metastatic CRC, one can divide them into those who have microsatellite instability (MSI)-high tumors and those who do not. MSI-high patients, which represent a minority of this patient population, seem to respond quite well immunotherapies such as PD-1/PD-L1 inhibitors, as their tumors are ridden with mutations, explains Bekaii-Saab.

The other, overwhelming majority of patients with CRC do not respond as well to immunotherapy agents. They do not have that same mutational load as the MSI-high patients, and thus do not have an immune-rich microenvironment, says Bekaii-Saab.

However, there are ways to manipulate the immune system to allow these patients to derive more clinical benefit from immunotherapy. One way that's currently being explored in the clinic in phase III trials is the application of a MEK inhibitor with PD-1 inhibitors. The MEK inhibitor can upregulate CD8 T cells found in the tumor microenvironment, and the 2 agents can work together to help these patients yield better responses.


Tanios Bekaii-Saab, MD, professor of Medicine, Mayo Clinic, discusses the role of immunotherapy in the treatment of patients with colorectal cancer (CRC).

When looking at patients with metastatic CRC, one can divide them into those who have microsatellite instability (MSI)-high tumors and those who do not. MSI-high patients, which represent a minority of this patient population, seem to respond quite well immunotherapies such as PD-1/PD-L1 inhibitors, as their tumors are ridden with mutations, explains Bekaii-Saab.

The other, overwhelming majority of patients with CRC do not respond as well to immunotherapy agents. They do not have that same mutational load as the MSI-high patients, and thus do not have an immune-rich microenvironment, says Bekaii-Saab.

However, there are ways to manipulate the immune system to allow these patients to derive more clinical benefit from immunotherapy. One way that's currently being explored in the clinic in phase III trials is the application of a MEK inhibitor with PD-1 inhibitors. The MEK inhibitor can upregulate CD8 T cells found in the tumor microenvironment, and the 2 agents can work together to help these patients yield better responses.



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