The key to cancer cells evading the immune system lies in a gene called SOX17.
MIT researchers discovered that the Sox17 protein, labeled in red, enables tumor cells to avoid immune detection by switching off the Lgr-5 protein, labeled in green.In a remarkable and positive breakthrough for cancer research, a team of MIT and Dana-Farber Cancer Institute researchers have discovered a crucial strategy that these elusive cells employ to avoid detection by the immune system.
SOX17’s betrayal doesn’t stop there. It also hinders the production of MHC proteins, which act like flags alerting the immune system to the presence of a cancerous cell. Further, it silences the cell’s production of chemokines – distress signals that typically recruit T cells to destroy the rogue cell.This discovery has ignited new hope in the fight against colon cancer. If doctors can find a way to switch SOX17 off or disrupt the pathway it triggers, early-stage cancers may lose their disguise.
Colon cancer often begins in intestinal stem cells, whose role is to continually regenerate the intestinal lining. These long-lived cancer cells are prone to accumulating mutations that can lead to the formation of precancerous polyps, which could eventually develop into metastatic colon cancer.organoids with SOX17 deactivated and implanted them into mice. This highlights the immense potential of targeting SOX17 as a way to catch and destroy colon cancer during its most vulnerable early stages.
“One of SOX17’s main roles is to turn off the interferon-gamma signaling pathway in colorectal cancer cells and precancerous adenoma cells. By turning off interferon-gamma receptor signaling in the tumor cells, the tumor cells become hidden from T cells and can grow in the presence of an immune system,” Yilmaz says.