Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, representing approximately 75-85% of all cases. Often considered preventable, primary liver cancer ranks as the sixth most frequently diagnosed cancer and the third leading cause of cancer deaths worldwide. Through a multi-institutional effort, researchers have identified activated ATF6α as a driver of HCC that suppresses immune defenses, predicts response to immune checkpoint therapy, and represents a potential target for intervention.