“To the immune system, foreign pathogens look very different from normal cells. But the difference with cancer cells isn’t as clear – except in microsatellite instability -high disease.
“Patients with MSI-high colorectal cancer are more likely to have their immune systems detect the tumors are different from normal tissue,” Kopetz says.
This helps lay the groundwork for immunotherapy to be effective. “The good news is the immune cells often recognize the cancer cells as different,” Kopetz says. “The barrier is the checkpoints – or the signals – that the tumor cells put on their surface to prevent the immune cells from attacking.”
This is where immune checkpoint inhibitors come in. They block the signal from the tumor cells that prevents the T cells from doing their work.
Unfortunately, only 3% of patients with metastatic colorectal cancer have MSI-high disease.
“It’s very low,” Kopetz says. “But for the first time, there’s a subset of patients where we can say, ‘Despite having metastatic disease, we can cure you with immunotherapy.’” He says that hasn’t been possible with chemotherapy and targeted therapies.