In a groundbreaking study published on November 21, 2024, researchers at Memorial Sloan Kettering Cancer Center (MSK) revealed how pancreatic cancer cells sidestep immune system detection by regulating retrotransposons—mobile genetic elements that can mimic viral threats.

Led by Drs. Benjamin Greenbaum and Siyu Sun, the team discovered that tumor cells balance the activity of two retrotransposon families—LINE-1 and SINEs—to avoid triggering the innate immune response. Normally, SINEs can produce double-stranded RNA (dsRNA), which resembles viral material and activates immune defenses. However, in pancreatic tumors, LINE-1 elements suppress SINE activity, preventing immune activation.

In cases where LINE-1 is absent, cancer cells deploy the ADAR1 protein to degrade dsRNA and maintain immune invisibility. Blocking either LINE-1 or ADAR1 in lab models led to reduced tumor growth, suggesting potential therapeutic targets.

This research not only deepens our understanding of tumor immune evasion but also opens avenues for novel treatments that could re-sensitize tumors to immune attack by disrupting their retrotransposon regulation.