The MYC protein has separable functions: its growth-promoting activity and its immune-evasion mechanism can be disentangled, suggesting a therapeutic angle in which inhibiting MYC’s RNA-binding capacity could expose tumors to immune attack without blocking its transcriptional roles in normal cells.

Blocking the immune-evading pathway offers a more precise cancer strategy than shutting down MYC entirely, since MYC’s essential roles in normal cells make total inhibition problematic.

The RNA-binding region responsible for immune silencing is distinct from the growth-promoting domain, enabling selective targeting that could disable immune evasion while preserving normal cell division.

Under stress, MYC relocates from DNA to nascent RNA, forms multimers around double-stranded RNA and R-loops, and recruits the nuclear exosome to degrade problematic RNA and prevent immune activation.

MYC binds nascent RNA during stress, forms multimeric clusters, and recruits the exosome to remove RNA-DNA hybrids, suppressing innate immune warnings and aiding tumor evasion.

In cell culture, both wild-type MYC and an RNA-binding–deficient mutant can drive proliferation, but only the wild-type MYC suppresses innate immune gene sets tied to NF-κB and interferon pathways.

Future work will determine how immune-activating RNA-DNA hybrids exit the nucleus and how MYC’s RNA-binding activity shapes the tumor microenvironment, with clinical applications still years away.

Funding for the research came from Cancer Research UK, the Children Cancer Free Foundation (Kika), INCa, and an ERC Advanced Grant.

The RNA-binding region RBRIII in MYC drives multimerization and RNA degradation without altering transcriptional activation, central to the immune-silencing process.

In an orthotopic mouse model, tumors with normal MYC grew rapidly, while those with the RBRIII mutant regressed dramatically in immunocompetent mice, highlighting immune recognition as a key driver of tumor regression when MYC’s RNA-binding function is disrupted.

The findings, published in Cell on January 22, 2026, come from a team led by Martin Eilers with collaborators from JMU, MIT, and Würzburg University Hospital, under Cancer Grand Challenges KOODAC.

The Cell paper identifies a novel function of MYC in pancreatic cancer, acting as an invisibility switch that dampens innate immune signaling.