NUS scientists uncover ‘hidden switch’ that helps cancer cells hide from the immune system

NUS scientists uncover 'hidden switch' that helps cancer cells hide from the immune system

Discovery challenges a long-held belief in RNA editing and opens a promising new avenue for cancer immunotherapy

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Researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) have uncovered a previously unknown mechanism that helps cancer cells evade detection by the body's immune system. The finding could pave the way for development of more effective cancer immunotherapies.

Published in Science Immunology on 12 June 2026, the study identifies the RNA helicase DDX6 as a previously unrecognised 'hidden switch' that prevents the immune system from recognising cancer cells. Targeting DDX6 could make tumours more visible to the immune system, improving existing or new immunotherapies.

Helping the immune system recognise cancer

Our immune system is constantly searching for abnormal cells, including cancer cells. One of the warning signals it looks for is double-stranded RNA (dsRNA), which are produced naturally within cells. Because these molecules resemble RNA produced during viral infections, they can trigger the innate immune system, which is the body's first line of defence against foreign or abnormal cells.

Many cancer cells suppress these warning signals, allowing them to grow unnoticed. Until now, scientists did not fully understand how this happened.

Previous studies have shown that ADAR1, an enzyme that edits RNA, helps regulate how cells respond to dsRNA. This study identifies the RNA helicase DDX6 as a previously unrecognised suppressor of dsRNA sensing.

Led by Associate Professor Polly Chen, Deputy Director and Principal Investigator of CSI Singapore, the team found that DDX6 works together with ADAR1 to suppress these natural danger signals. As a result, DDX6 reduces immune activation triggered by endogenous dsRNA, hence making cancer cells much less visible to the immune system.

These findings provide new insights into how anti-tumour immune responses are regulated.

"Cancer cells are remarkably good at hiding from the immune system. Our study uncovered a previously unknown mechanism that helps them stay hidden. By targeting DDX6, we may be able to remove this 'cloak' and enable the immune system to recognise and attack cancer more effectively. Beyond its therapeutic potential, this work also changes our understanding of how RNA editing regulates immune responses," explained Assoc Prof Chen, the lead author for this study.

Challenging a long-held view of RNA editing

For many years, the prevailing view was that RNA editing weakened the structure of dsRNA, making it less likely to trigger immune responses. Instead, the CSI Singapore team found that certain RNA editing events can instead strengthen dsRNA structures, enhancing their ability to activate the body's natural immune defences. DDX6 prevents these beneficial RNA editing events from occurring, helping tumours escape immune attack.

This new framework for understanding how RNA editing regulates immune sensing in cancer fundamentally changes how researchers think about RNA editing and its role in regulating immunity.

"What surprised us most was that the biology did not behave the way we expected. For years, researchers believed RNA editing generally weakened these immune-triggering RNA molecules. Instead, we found that certain RNA editing events can actually strengthen them. This completely changes how we think about the relationship between RNA editing and immune activation, and opens up exciting new possibilities for developing cancer therapies," Dr Larry Ng, first author for this paper and Research Fellow at CSI Singapore.

Potential implications for cancer immunotherapy

The discovery identifies a novel mechanism of cancer immune evasion and highlights DDX6 as a potential new target for cancer immunotherapy. Targeting this pathway could help overcome cancer-associated immunosuppression and potentially improve the effectiveness of existing cancer immunotherapies. In laboratory studies, removing DDX6 restored immune signalling and slowed tumour growth by allowing cancer cells to become more visible to the immune system.

The research team is now working to identify molecules that block DDX6 and investigate their ability to enhance anti-tumour immune responses. In parallel, the researchers plan to identify additional proteins involved in this newly discovered pathway and determine how they contribute to cancer-associated immunosuppression. Together, these efforts could uncover additional therapeutic targets that could strengthen anti-tumour immunity.