Understanding Viral Mimicry in Cancer Cells and Its Impact on Immune Response

Recent research sheds light on how repetitive DNA sequences within cancer cells can mimic viral patterns, triggering an immune response that influences cancer development and progression. This phenomenon, known as "viral mimicry," occurs when dormant or inactive repetitive DNA elements—comprising nearly half of the human genome—are activated, producing RNA molecules resembling viral genetic material.

Benjamin Greenbaum, Ph.D., a computational oncologist from Memorial Sloan Kettering Cancer Center, has dedicated his work to understanding how the immune system detects and responds to these molecular patterns during cancer evolution. These pathogen-associated molecular patterns (PAMPs) serve as signals that can prompt immune activation, even though they originate from the body's own cells.

The Greenbaum lab has developed advanced mathematical models that utilize principles from statistical physics, machine learning, and evolutionary dynamics to quantify viral mimicry. This innovative approach helps identify which DNA sequences activate immune responses and why certain repetitive elements persist in the genome. Their findings suggest that some repetitive DNA may serve a protective role against viral infections or indicate cellular dysfunction.

Published in Cell Genomics in September 2025, this research provides a new framework for understanding innate immunity's role in cancer. Notably, the team discovered specific classes of repetitive DNA elements that effectively mimic viruses, hinting at their potential purpose in antiviral defense. Interestingly, these mimicry signals could also mark cells as abnormal, alerting the immune system to cellular damage.

This research has significant implications for cancer immunotherapy, including the design of vaccines and therapies that modulate immune detection. Improving our understanding of immune activation mechanisms could lead to more effective treatments that enhance how the immune system recognizes and fights cancer cells.

In previous studies, the team revealed how pancreatic cancer cells evade immune attack by managing DNA repeats called retrotransposons. The mathematical approaches from this research promise to uncover further insights into innate immunity's influence on various cancers, ultimately guiding the development of novel immunotherapies and diagnostic tools.